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Current Neuropharmacology


ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

General Review Article

Statins and the Brain: More than Lipid Lowering Agents?

Author(s): Anna Fracassi , Martina Marangoni, Pamela Rosso, Valentina Pallottini, Marco Fioramonti, Silvia Siteni and Marco Segatto*

Volume 17, Issue 1, 2019

Page: [59 - 83] Pages: 25

DOI: 10.2174/1570159X15666170703101816

Price: $65


Background: Statins represent a class of medications widely prescribed to efficiently treat dyslipidemia. These drugs inhibit 3-βhydroxy 3β-methylglutaryl Coenzyme A reductase (HMGR), the rate-limiting enzyme of mevalonate (MVA) pathway. Besides cholesterol, MVA pathway leads to the production of several other compounds, which are essential in the regulation of a plethora of biological activities, including in the central nervous system. For these reasons, statins are able to induce pleiotropic actions, and acquire increased interest as potential and novel modulators in brain processes, especially during pathological conditions.

Objective: The purpose of this review is to summarize and examine the current knowledge about pharmacokinetic and pharmacodynamic properties of statins in the brain. In addition, effects of statin on brain diseases are discussed providing the most up-to-date information.

Methods: Relevant scientific information was identified from PubMed database using the following keywords: statins and brain, central nervous system, neurological diseases, neurodegeneration, brain tumors, mood, stroke.

Results: 315 scientific articles were selected and analyzed for the writing of this review article. Several papers highlighted that statin treatment is effective in preventing or ameliorating the symptomatology of a number of brain pathologies. However, other studies failed to demonstrate a neuroprotective effect.

Conclusion: Even though considerable research studies suggest pivotal functional outcomes induced by statin therapy, additional investigation is required to better determine the pharmacological effectiveness of statins in the brain, and support their clinical use in the management of different neuropathologies.

Keywords: Statins, brain, neurodegeneration, neurological disorders, mood, brain tumors.

Graphical Abstract
Sirtori, C.R. The pharmacology of statins. Pharmacol. Res., 2014, 88, 3-11. [].
Segatto, M.; Leboffe, L.; Trapani, L.; Pallottini, V. Cholesterol homeostasis failure in the brain: implications for synaptic dysfunction and cognitive decline. Curr. Med. Chem., 2014, 21(24), 2788-2802. [].
Trapani, L.; Segatto, M.; Pallottini, V. Regulation and deregulation of cholesterol homeostasis: The liver as a metabolic “power station”. World J. Hepatol., 2012, 4(6), 184-190. [ 10.4254/wjh.v4.i6.184].
Espenshade, P.J.; Hughes, A.L. Regulation of sterol synthesis in eukaryotes. Annu. Rev. Genet., 2007, 41, 401-427. [http://dx.doi. org/10.1146/annurev.genet.41.110306.130315].
Marino, M.; di Masi, A.; Trezza, V.; Pallottini, V.; Polticelli, F.; Ascenzi, P. Xenosensors CAR and PXR at work: impact on statin metabolism. Curr. Drug Metab., 2011, 12(3), 300-311. [http://dx.].
Corsini, A.; Maggi, F.M.; Catapano, A.L. Pharmacology of competitive inhibitors of HMG-CoA reductase. Pharmacol. Res., 1995, 31(1), 9-27. [].
Neuvonen, P.J. Drug interactions with HMG-CoA reductase inhibitors (statins): the importance of CYP enzymes, transporters and pharmacogenetics. Curr. Opin. Investig. Drugs, 2010, 11(3), 323-332.
Neuvonen, P.J.; Niemi, M.; Backman, J.T. Drug interactions with lipid-lowering drugs: mechanisms and clinical relevance. Clin. Pharmacol. Ther., 2006, 80(6), 565-581. [ j.clpt.2006.09.003].
Lennernas, H.; Fager, G. Pharmacodynamics and pharmacokinetics of the HMG-CoA reductase inhibitors. Similarities and differences. Clin. Pharmacokinet., 1997, 32(5), 403-425. [ 2165/00003088-199732050-00005].
Williams, D.; Feely, J. Pharmacokinetic-pharmacodynamic drug interactions with HMG-CoA reductase inhibitors. Clin. Pharmacokinet., 2002, 41(5), 343-370. [].
Christians, U.; Jacobsen, W.; Floren, L.C. Metabolism and drug interactions of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors in transplant patients: are the statins mechanistically similar? Pharmacol. Ther., 1998, 80(1), 1-34. [ 1016/S0163-7258(98)00016-3].
Quion, J.A.; Jones, P.H. Clinical pharmacokinetics of pravastatin. Clin. Pharmacokinet., 1994, 27(2), 94-103. [ 2165/00003088-199427020-00002].
Hamelin, B.A.; Turgeon, J. Hydrophilicity/lipophilicity: relevance for the pharmacology and clinical effects of HMG-CoA reductase inhibitors. Trends Pharmacol. Sci., 1998, 19(1), 26-37. [http://dx.].
Schachter, M. Chemical, pharmacokinetic and pharmacodynamic properties of statins: an update. Fundam. Clin. Pharmacol., 2005, 19(1), 117-125. [].
Kivisto, K.T.; Niemi, M. Influence of drug transporter polymorphisms on pravastatin pharmacokinetics in humans. Pharm. Res., 2007, 24(2), 239-247. [].
Kitamura, S.; Maeda, K.; Wang, Y.; Sugiyama, Y. Involvement of multiple transporters in the hepatobiliary transport of rosuvastatin. Drug Metab. Dispos., 2008, 36(10), 2014-2023. [ 10.1124/dmd.108.021410].
Trapani, L.; Melli, L.; Segatto, M.; Trezza, V.; Campolongo, P.; Jozwiak, A.; Swiezewska, E.; Pucillo, L.P.; Moreno, S.; Fanelli, F.; Linari, M.; Pallottini, V. Effects of myosin heavy chain (MHC) plasticity induced by HMGCoA-reductase inhibition on skeletal muscle functions. FASEB J., 2011, 25(11), 4037-4047. [http://dx.].
Trapani, L.; Segatto, M.; Ascenzi, P.; Pallottini, V. Potential role of nonstatin cholesterol lowering agents. IUBMB Life, 2011, 63(11), 964-971. [].
Trapani, L.; Segatto, M.; La Rosa, P.; Fanelli, F.; Moreno, S.; Marino, M.; Pallottini, V. 3-hydroxy 3-methylglutaryl coenzyme A reductase inhibition impairs muscle regeneration. J. Cell. Biochem., 2012, 113(6), 2057-2063. [].
Tonelli, M.; Moye, L.; Sacks, F.M.; Cole, T.; Curhan, G.C. Effect of pravastatin on loss of renal function in people with moderate chronic renal insufficiency and cardiovascular disease. J. Am. Soc. Nephrol., 2003, 14(6), 1605-1613. [ ASN.0000068461.45784.2F].
Vidt, D.G.; Cressman, M.D.; Harris, S.; Pears, J.S.; Hutchinson, H.G. Rosuvastatin-induced arrest in progression of renal disease. Cardiology, 2004, 102(1), 52-60. [ 000077704].
Chopra, V.; Rogers, M.A.; Buist, M.; Govindan, S.; Lindenauer, P.K.; Saint, S.; Flanders, S.A. Is statin use associated with reduced mortality after pneumonia? A systematic review and meta-analysis. Am. J. Med., 2012, 125(11), 1111-1123. [ j.amjmed.2012.04.011].
Novack, V.; MacFadyen, J.; Malhotra, A.; Almog, Y.; Glynn, R.J.; Ridker, P.M. The effect of rosuvastatin on incident pneumonia: results from the JUPITER trial. CMAJ, 2012, 184(7), E367-E372. [].
Chataway, J.; Schuerer, N.; Alsanousi, A.; Chan, D.; MacManus, D.; Hunter, K.; Anderson, V.; Bangham, C.R.; Clegg, S.; Nielsen, C.; Fox, N.C.; Wilkie, D.; Nicholas, J.M.; Calder, V.L.; Greenwood, J.; Frost, C.; Nicholas, R. Effect of high-dose simvastatin on brain atrophy and disability in secondary progressive multiple sclerosis (MS-STAT): a randomised, placebo-controlled, phase 2 trial. Lancet, 2014, 383(9936), 2213-2221. [http://dx.doi. org/10.1016/S0140-6736(13)62242-4].
Preiss, D.; Tikkanen, M.J.; Welsh, P.; Ford, I.; Lovato, L.C.; Elam, M.B.; LaRosa, J.C.; DeMicco, D.A.; Colhoun, H.M.; Goldenberg, I.; Murphy, M.J.; MacDonald, T.M.; Pedersen, T.R.; Keech, A.C.; Ridker, P.M.; Kjekshus, J.; Sattar, N.; McMurray, J.J. Lipid-modifying therapies and risk of pancreatitis: a meta-analysis. JAMA, 2012, 308(8), 804-811. [ 2012.8439].
El-Sisi, A.A.; Hegazy, S.K.; Salem, K.A. AbdElkawy, K. S. Atorvastatin improves erectile dysfunction in patients initially irresponsive to Sildenafil by the activation of endothelial nitric oxide synthase. Int. J. Impot. Res., 2013, 25(4), 143-148. [http://dx.doi. org/10.1038/ijir.2012.46].
Subramanian, S.; Emami, H.; Vucic, E.; Singh, P.; Vijayakumar, J.; Fifer, K.M.; Alon, A.; Shankar, S.S.; Farkouh, M.; Rudd, J.H.; Fayad, Z.A.; Van Dyke, T.E.; Tawakol, A. High-dose atorvastatin reduces periodontal inflammation: a novel pleiotropic effect of statins. J. Am. Coll. Cardiol., 2013, 62(25), 2382-2391. [].
Cartocci, V.; Servadio, M.; Trezza, V.; Pallottini, V. Can cholesterol metabolism modulation affect brain function and behavior? J. Cell. Physiol., 2017, 232(2), 281-286. [ jcp.25488].
Horton, J.D. Sterol regulatory element-binding proteins: transcriptional activators of lipid synthesis. Biochem. Soc. Trans., 2002, 30(Pt 6), 1091-1095. [].
Segatto, M.; Trapani, L.; Marino, M.; Pallottini, V. Age- and sex-related differences in extra-hepatic low-density lipoprotein receptor. J. Cell. Physiol., 2011, 226(10), 2610-2616. [ 10.1002/jcp.22607].
Segatto, M.; Trapani, L.; Lecis, C.; Pallottini, V. Regulation of cholesterol biosynthetic pathway in different regions of the rat central nervous system. Acta Physiol. (Oxf.), 2012, 206(1), 62-71. [].
Pfrieger, F.W. Role of cholesterol in synapse formation and function. Biochim. Biophys. Acta, 2003, 1610(2), 271-280. [http://dx.].
Bjorkhem, I.; Meaney, S. Brain cholesterol: long secret life behind a barrier. Arterioscler. Thromb. Vasc. Biol., 2004, 24(5), 806-815. [].
Snipes, G.J.; Orfali, W. Common themes in peripheral neuropathy disease genes. Cell Biol. Int., 1998, 22(11-12), 815-835. [http://dx.].
Goritz, C.; Mauch, D.H.; Pfrieger, F.W. Multiple mechanisms mediate cholesterol-induced synaptogenesis in a CNS neuron. Mol. Cell. Neurosci., 2005, 29(2), 190-201. [ j.mcn.2005.02.006].
Pfrieger, F.W. Outsourcing in the brain: do neurons depend on cholesterol delivery by astrocytes? BioEssays, 2003, 25(1), 72-78. [].
Shanmugaratnam, J.; Berg, E.; Kimerer, L.; Johnson, R.J.; Amaratunga, A.; Schreiber, B.M.; Fine, R.E. Retinal muller glia secrete apolipoproteins E and J which are efficiently assembled into lipoprotein particles. Brain Res. Mol. Brain Res., 1997, 50(1-2), 113-120. [].
Oram, J.F.; Heinecke, J.W. ATP-binding cassette transporter A1: a cell cholesterol exporter that protects against cardiovascular disease. Physiol. Rev., 2005, 85(4), 1343-1372. [ 10.1152/physrev.00005.2005].
Segatto, M.; Di Giovanni, A.; Marino, M.; Pallottini, V. Analysis of the protein network of cholesterol homeostasis in different brain regions: an age and sex dependent perspective. J. Cell. Physiol., 2013, 228(7), 1561-1567. [].
Ohvo-Rekila, H.; Ramstedt, B.; Leppimaki, P.; Slotte, J.P. Cholesterol interactions with phospholipids in membranes. Prog. Lipid Res., 2002, 41(1), 66-97. [ (01)00020-0].
Saher, G.; Brugger, B.; Lappe-Siefke, C.; Mobius, W.; Tozawa, R.; Wehr, M.C.; Wieland, F.; Ishibashi, S.; Nave, K.A. High cholesterol level is essential for myelin membrane growth. Nat. Neurosci., 2005, 8(4), 468-475. [].
Haines, T.H. Do sterols reduce proton and sodium leaks through lipid bilayers? Prog. Lipid Res., 2001, 40(4), 299-324. [http://dx.].
Deutsch, J.W.; Kelly, R.B. Lipids of synaptic vesicles: relevance to the mechanism of membrane fusion. Biochemistry, 1981, 20(2), 378-385. [].
Huttner, W.B.; Zimmerberg, J. Implications of lipid microdomains for membrane curvature, budding and fission. Curr. Opin. Cell Biol., 2001, 13(4), 478-484. [ (00)00239-8].
Mitter, D.; Reisinger, C.; Hinz, B.; Hollmann, S.; Yelamanchili, S.V.; Treiber-Held, S.; Ohm, T.G.; Herrmann, A.; Ahnert-Hilger, G. The synaptophysin/synaptobrevin interaction critically depends on the cholesterol content. J. Neurochem., 2003, 84(1), 35-42. [].
Sooksawate, T.; Simmonds, M.A. Effects of membrane cholesterol on the sensitivity of the GABA(A) receptor to GABA in acutely dissociated rat hippocampal neurones. Neuropharmacology, 2001, 40(2), 178-184. [].
Hering, H.; Lin, C.C.; Sheng, M. Lipid rafts in the maintenance of synapses, dendritic spines, and surface AMPA receptor stability. J. Neurosci., 2003, 23(8), 3262-3271. [ JNEUROSCI.23-08-03262.2003].
Zipp, F.; Waiczies, S.; Aktas, O.; Neuhaus, O.; Hemmer, B.; Schraven, B.; Nitsch, R.; Hartung, H.P. Impact of HMG-CoA reductase inhibition on brain pathology. Trends Pharmacol. Sci., 2007, 28(7), 342-349. [].
Lecis, C.; Segatto, M. Cholesterol Homeostasis Imbalance and Brain Functioning: Neuro-logical Disorders and Behavioral Consequences. J. Neurol. Neurol. Disord., 2014, 1(1), 101.
Buchovecky, C.M.; Turley, S.D.; Brown, H.M.; Kyle, S.M.; McDonald, J.G.; Liu, B.; Pieper, A.A.; Huang, W.; Katz, D.M.; Russell, D.W.; Shendure, J.; Justice, M.J. A suppressor screen in Mecp2 mutant mice implicates cholesterol metabolism in Rett syndrome. Nat. Genet., 2013, 45(9), 1013-1020. [ 1038/ng.2714].
Kyle, S.M.; Saha, P.K.; Brown, H.M.; Chan, L.C.; Justice, M.J. MeCP2 co-ordinates liver lipid metabolism with the NCoR1/ HDAC3 corepressor complex. Hum. Mol. Genet., 2016, 25(14), 3029-3041.
Lopez, A.M.; Chuang, J.C.; Posey, K.S.; Turley, S.D. ‘Corrigenda to “Suppression of brain cholesterol synthesis in male Mecp2-deficient mice is age dependent and not accompanied by a concurrent change in the rate of fatty acid synthesis” [Brain Res. 1654 (2017) 77-84]’. Brain Res., 2017, 1657, 383. [ 1016/j.brainres.2016.12.016].
Sticozzi, C.; Belmonte, G.; Pecorelli, A.; Cervellati, F.; Leoncini, S.; Signorini, C.; Ciccoli, L.; De Felice, C.; Hayek, J.; Valacchi, G. Scavenger receptor B1 post-translational modifications in Rett syndrome. FEBS Lett., 2013, 587(14), 2199-2204. [ 10.1016/j.febslet.2013.05.042].
Segatto, M.; Trapani, L.; Di Tunno, I.; Sticozzi, C.; Valacchi, G.; Hayek, J.; Pallottini, V. Cholesterol metabolism is altered in Rett syndrome: a study on plasma and primary cultured fibroblasts derived from patients. PLoS One, 2014, 9(8), e104834. [http://dx.].
Pecorelli, A.; Belmonte, G.; Meloni, I.; Cervellati, F.; Gardi, C.; Sticozzi, C.; De Felice, C.; Signorini, C.; Cortelazzo, A.; Leoncini, S.; Ciccoli, L.; Renieri, A.; Jay Forman, H.; Hayek, J.; Valacchi, G. Alteration of serum lipid profile, SRB1 loss, and impaired Nrf2 activation in CDKL5 disorder. Free Radic. Biol. Med., 2015, 86, 156-165. [].
Matthews, R.T.; Yang, L.; Browne, S.; Baik, M.; Beal, M.F. Coenzyme Q10 administration increases brain mitochondrial concentrations and exerts neuroprotective effects. Proc. Natl. Acad. Sci. USA, 1998, 95(15), 8892-8897. [ 15.8892].
Young, A.J.; Johnson, S.; Steffens, D.C.; Doraiswamy, P.M. Coenzyme Q10: a review of its promise as a neuroprotectant. CNS Spectr., 2007, 12(1), 62-68. [ 00020538].
Quinzii, C.M.; Hirano, M. Coenzyme Q and mitochondrial disease. Dev. Disabil. Res. Rev., 2010, 16(2), 183-188. [ 1002/ddrr.108].
Barca, E.; Kleiner, G.; Tang, G.; Ziosi, M.; Tadesse, S.; Masliah, E.; Louis, E.D.; Faust, P.; Kang, U.J.; Torres, J.; Cortes, E.P.; Vonsattel, J.P.; Kuo, S.H.; Quinzii, C.M. Decreased coenzyme Q10 levels in multiple system atrophy cerebellum. J. Neuropathol. Exp. Neurol., 2016, 75(7), 663-672. [ jnen/nlw037].
Schottlaender, L.V.; Bettencourt, C.; Kiely, A.P.; Chalasani, A.; Neergheen, V.; Holton, J.L.; Hargreaves, I.; Houlden, H. Coenzyme Q10 levels are decreased in the cerebellum of multiple-system atrophy patients. PLoS One, 2016, 11(2), e0149557. [].
Stefely, J.A.; Licitra, F.; Laredj, L.; Reidenbach, A.G.; Kemmerer, Z.A.; Grangeray, A.; Jaeg-Ehret, T.; Minogue, C.E.; Ulbrich, A.; Hutchins, P.D.; Wilkerson, E.M.; Ruan, Z.; Aydin, D.; Hebert, A.S.; Guo, X.; Freiberger, E.C.; Reutenauer, L.; Jochem, A.; Chergova, M.; Johnson, I.E.; Lohman, D.C.; Rush, M.J.; Kwiecien, N.W.; Singh, P.K.; Schlagowski, A.I.; Floyd, B.J.; Forsman, U.; Sindelar, P.J.; Westphall, M.S.; Pierrel, F.; Zoll, J.; Dal Peraro, M.; Kannan, N.; Bingman, C.A.; Coon, J.J.; Isope, P.; Puccio, H.; Pagliarini, D.J. Cerebellar ataxia and coenzyme Q deficiency through loss of unorthodox kinase activity. Mol. Cell, 2016, 63(4), 608-620. [].
Segatto, M.; Manduca, A.; Lecis, C.; Rosso, P.; Jozwiak, A.; Swiezewska, E.; Moreno, S.; Trezza, V.; Pallottini, V. Simvastatin treatment highlights a new role for the isoprenoid/cholesterol biosynthetic pathway in the modulation of emotional reactivity and cognitive performance in rats. Neuropsychopharmacology, 2014, 39(4), 841-854. [].
Mazzucchelli, C.; Brambilla, R. Ras-related and MAPK signalling in neuronal plasticity and memory formation. Cell. Mol. Life Sci., 2000, 57(4), 604-611. [].
Bender, R.H.; Haigis, K.M.; Gutmann, D.H. Activated k-ras, but not h-ras or N-ras, regulates brain neural stem cell proliferation in a raf/rb-dependent manner. Stem Cells, 2015, 33(6), 1998-2010. [].
Park, J.C.; Jeong, W.J.; Kim, M.Y.; Min, D.; Choi, K.Y. Retinoic-acid-mediated HRas stabilization induces neuronal differentiation of neural stem cells during brain development. J. Cell Sci., 2016, 129(15), 2997-3007. [].
Tidyman, W.E.; Rauen, K.A. The RASopathies: developmental syndromes of Ras/MAPK pathway dysregulation. Curr. Opin. Genet. Dev., 2009, 19(3), 230-236. [ 2009.04.001].
Lingor, P.; Teusch, N.; Schwarz, K.; Mueller, R.; Mack, H.; Bahr, M.; Mueller, B.K. Inhibition of Rho kinase (ROCK) increases neurite outgrowth on chondroitin sulphate proteoglycan in vitro and axonal regeneration in the adult optic nerve in vivo. J. Neurochem., 2007, 103(1), 181-189.
Cartocci, V.; Segatto, M.; Di Tunno, I.; Leone, S.; Pfrieger, F.W.; Pallottini, V. Modulation of the isoprenoid/cholesterol biosynthetic pathway during neuronal differentiation In Vitro. J. Cell. Biochem., 2016, 117(9), 2036-2044. [].
Ramakers, G.J. Rho proteins, mental retardation and the cellular basis of cognition. Trends Neurosci., 2002, 25(4), 191-199. [].
Lin, G.N.; Corominas, R.; Lemmens, I.; Yang, X.; Tavernier, J.; Hill, D.E.; Vidal, M.; Sebat, J.; Iakoucheva, L.M. Spatiotemporal 16p11.2 protein network implicates cortical late mid-fetal brain development and KCTD13-Cul3-RhoA pathway in psychiatric diseases. Neuron, 2015, 85(4), 742-754. [ j.neuron.2015.01.010].
Narayanan, K.L.; Chopra, V.; Rosas, H.D.; Malarick, K.; Hersch, S. Rho kinase pathway alterations in the brain and leukocytes in Huntington’s Disease. Mol. Neurobiol., 2016, 53(4), 2132-2140. [].
Henderson, B.W.; Gentry, E.G.; Rush, T.; Troncoso, J.C.; Thambisetty, M.; Montine, T.J.; Herskowitz, J.H. Rho-associated protein kinase 1 (ROCK1) is increased in Alzheimer’s disease and ROCK1 depletion reduces amyloid-beta levels in brain. J. Neurochem., 2016, 138(4), 525-531. [].
Takai, Y.; Sasaki, T.; Matozaki, T. Small GTP-binding proteins. Physiol. Rev., 2001, 81(1), 153-208. [ 2001.81.1.153].
Geppert, M.; Sudhof, T.C. RAB3 and synaptotagmin: the yin and yang of synaptic membrane fusion. Annu. Rev. Neurosci., 1998, 21, 75-95. [].
Cheng, Y.; Wang, J.; Wang, Y.; Ding, M. Synaptotagmin 1 directs repetitive release by coupling vesicle exocytosis to the Rab3 cycle. eLife, 2015, 4, 1-19.
Andriamampandry, C.; Muller, C.; Schmidt-Mutter, C.; Gobaille, S.; Spedding, M.; Aunis, D.; Maitre, M. Mss4 gene is up-regulated in rat brain after chronic treatment with antidepressant and down-regulated when rats are anhedonic. Mol. Pharmacol., 2002, 62(6), 1332-1338. [].
Baskys, A.; Bayazitov, I.; Zhu, E.; Fang, L.; Wang, R. Rab-mediated endocytosis: linking neurodegeneration, neuroprotection, and synaptic plasticity? Ann. N. Y. Acad. Sci., 2007, 1122, 313-329. [].
Blaveri, E.; Kelly, F.; Mallei, A.; Harris, K.; Taylor, A.; Reid, J.; Razzoli, M.; Carboni, L.; Piubelli, C.; Musazzi, L.; Racagni, G.; Mathe, A.; Popoli, M.; Domenici, E.; Bates, S. Expression profiling of a genetic animal model of depression reveals novel molecular pathways underlying depressive-like behaviours. PLoS One, 2010, 5(9), e12596. [].
Dalfo, E.; Barrachina, M.; Rosa, J.L.; Ambrosio, S.; Ferrer, I. Abnormal alpha-synuclein interactions with rab3a and rabphilin in diffuse Lewy body disease. Neurobiol. Dis., 2004, 16(1), 92-97. [].
Aligianis, I.A.; Johnson, C.A.; Gissen, P.; Chen, D.; Hampshire, D.; Hoffmann, K.; Maina, E.N.; Morgan, N.V.; Tee, L.; Morton, J.; Ainsworth, J.R.; Horn, D.; Rosser, E.; Cole, T.R.; Stolte-Dijkstra, I.; Fieggen, K.; Clayton-Smith, J.; Megarbane, A.; Shield, J.P.; Newbury-Ecob, R.; Dobyns, W.B.; Graham, J.M., Jr; Kjaer, K.W.; Warburg, M.; Bond, J.; Trembath, R.C.; Harris, L.W.; Takai, Y.; Mundlos, S.; Tannahill, D.; Woods, C.G.; Maher, E.R. Mutations of the catalytic subunit of RAB3GAP cause Warburg Micro syndrome. Nat. Genet., 2005, 37(3), 221-223. [ 1038/ng1517].
Aligianis, I.A.; Morgan, N.V.; Mione, M.; Johnson, C.A.; Rosser, E.; Hennekam, R.C.; Adams, G.; Trembath, R.C.; Pilz, D.T.; Stoodley, N.; Moore, A.T.; Wilson, S.; Maher, E.R. Mutation in Rab3 GTPase-activating protein (RAB3GAP) noncatalytic subunit in a kindred with Martsolf syndrome. Am. J. Hum. Genet., 2006, 78(4), 702-707. [].
D’Adamo, P.; Menegon, A.; Lo Nigro, C.; Grasso, M.; Gulisano, M.; Tamanini, F.; Bienvenu, T.; Gedeon, A.K.; Oostra, B.; Wu, S.K.; Tandon, A.; Valtorta, F.; Balch, W.E.; Chelly, J.; Toniolo, D. Mutations in GDI1 are responsible for X-linked non-specific mental retardation. Nat. Genet., 1998, 19(2), 134-139. [http://dx.doi. org/10.1038/487].
Morava, E.; Wevers, R.A.; Cantagrel, V.; Hoefsloot, L.H.; Al-Gazali, L.; Schoots, J.; van Rooij, A.; Huijben, K.; van Ravenswaaij-Arts, C.M.; Jongmans, M.C.; Sykut-Cegielska, J.; Hoffmann, G.F.; Bluemel, P.; Adamowicz, M.; van Reeuwijk, J.; Ng, B.G.; Bergman, J.E.; van Bokhoven, H.; Korner, C.; Babovic-Vuksanovic, D.; Willemsen, M.A.; Gleeson, J.G.; Lehle, L.; de Brouwer, A.P.; Lefeber, D.J. A novel cerebello-ocular syndrome with abnormal glycosylation due to abnormalities in dolichol metabolism. Brain, 2011, 133(11), 3210-3220. [ 10.1093/brain/awq261].
Johnson-Anuna, L.N.; Eckert, G.P.; Keller, J.H.; Igbavboa, U.; Franke, C.; Fechner, T.; Schubert-Zsilavecz, M.; Karas, M.; Muller, W.E.; Wood, W.G. Chronic administration of statins alters multiple gene expression patterns in mouse cerebral cortex. J. Pharmacol. Exp. Ther., 2005, 312(2), 786-793. [ 10.1124/jpet.104.075028].
Hsiang, B.; Zhu, Y.; Wang, Z.; Wu, Y.; Sasseville, V.; Yang, W.P.; Kirchgessner, T.G. A novel human hepatic organic anion transporting polypeptide (OATP2). Identification of a liver-specific human organic anion transporting polypeptide and identification of rat and human hydroxymethylglutaryl-CoA reductase inhibitor transporters. J. Biol. Chem., 1999, 274(52), 37161-37168. [ 10.1074/jbc.274.52.37161].
Lee, G.; Dallas, S.; Hong, M.; Bendayan, R. Drug transporters in the central nervous system: brain barriers and brain parenchyma considerations. Pharmacol. Rev., 2001, 53(4), 569-596. [http://dx.].
Nagasawa, K.; Nagai, K.; Sumitani, Y.; Moriya, Y.; Muraki, Y.; Takara, K.; Ohnishi, N.; Yokoyama, T.; Fujimoto, S. Monocarboxylate transporter mediates uptake of lovastatin acid in rat cultured mesangial cells. J. Pharm. Sci., 2002, 91(12), 2605-2613. [].
Vijay, N.; Morris, M.E. Role of monocarboxylate transporters in drug delivery to the brain. Curr. Pharm. Des., 2014, 20(10), 1487-1498. [].
Tsuji, A.; Saheki, A.; Tamai, I.; Terasaki, T. Transport mechanism of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors at the blood-brain barrier. J. Pharmacol. Exp. Ther., 1993, 267(3), 1085-1090.
Pierre, K.; Pellerin, L. Monocarboxylate transporters in the central nervous system: distribution, regulation and function. J. Neurochem., 2005, 94(1), 1-14. [ 2005.03168.x].
Lutjohann, D.; Stroick, M.; Bertsch, T.; Kuhl, S.; Lindenthal, B.; Thelen, K.; Andersson, U.; Bjorkhem, I.; Bergmann Kv, K.; Fassbender, K. High doses of simvastatin, pravastatin, and cholesterol reduce brain cholesterol synthesis in guinea pigs. Steroids, 2004, 69(6), 431-438. [].
Ostrowski, S.M.; Johnson, K.; Siefert, M.; Shank, S.; Sironi, L.; Wolozin, B.; Landreth, G.E.; Ziady, A.G. Simvastatin inhibits protein isoprenylation in the brain. Neuroscience, 2016, 329, 264-274. [].
Nothdurfter, C.; Tanasic, S.; Di Benedetto, B.; Rammes, G.; Wagner, E.M.; Kirmeier, T.; Ganal, V.; Kessler, J.S.; Rein, T.; Holsboer, F.; Rupprecht, R. Impact of lipid raft integrity on 5-HT3 receptor function and its modulation by antidepressants. Neuropsychopharmacology, 2010, 35(7), 1510-1519. [ 1038/npp.2010.20].
Shrivastava, S.; Pucadyil, T.J.; Paila, Y.D.; Ganguly, S.; Chattopadhyay, A. Chronic cholesterol depletion using statin impairs the function and dynamics of human serotonin(1A) receptors. Biochemistry, 2010, 49(26), 5426-5435. [ bi100276b].
Ponce, J.; de la Ossa, N.P.; Hurtado, O.; Millan, M.; Arenillas, J.F.; Davalos, A.; Gasull, T. Simvastatin reduces the association of NMDA receptors to lipid rafts: a cholesterol-mediated effect in neuroprotection. Stroke, 2008, 39(4), 1269-1275. [ 10.1161/STROKEAHA.107.498923].
Tong, X.K.; Lecrux, C.; Rosa-Neto, P.; Hamel, E. Age-dependent rescue by simvastatin of Alzheimer’s disease cerebrovascular and memory deficits. J. Neurosci., 2012, 32(14), 4705-4715. [http://dx.].
Mans, R.A.; McMahon, L.L.; Li, L. Simvastatin-mediated enhancement of long-term potentiation is driven by farnesyl-pyrophosphate depletion and inhibition of farnesylation. Neuroscience, 2012, 202, 1-9. [ 2011.12.007].
Roy, A.; Jana, M.; Kundu, M.; Corbett, G.T.; Rangaswamy, S.B.; Mishra, R.K.; Luan, C.H.; Gonzalez, F.J.; Pahan, K. HMG-CoA reductasei bind to PPARalpha to upregulate neurotrophin Expression in the brain and improve memory in mice. Cell Metab., 2015, 22(2), 253-265. [].
Lu, D.; Qu, C.; Goussev, A.; Jiang, H.; Lu, C.; Schallert, T.; Mahmood, A.; Chen, J.; Li, Y.; Chopp, M. Statins increase neurogenesis in the dentate gyrus, reduce delayed neuronal death in the hippocampal CA3 region, and improve spatial learning in rat after traumatic brain injury. J. Neurotrauma, 2007, 24(7), 1132-1146. [].
Robin, N.C.; Agoston, Z.; Biechele, T.L.; James, R.G.; Berndt, J.D.; Moon, R.T. Simvastatin promotes adult hippocampal neurogenesis by enhancing Wnt/beta-catenin signaling. Stem Cell Reports, 2013, 2(1), 9-17. [ 002].
Wu, H.; Lu, D.; Jiang, H.; Xiong, Y.; Qu, C.; Li, B.; Mahmood, A.; Zhou, D.; Chopp, M. Simvastatin-mediated upregulation of VEGF and BDNF, activation of the PI3K/Akt pathway, and increase of neurogenesis are associated with therapeutic improvement after traumatic brain injury. J. Neurotrauma, 2008, 25(2), 130-139. [].
Li, H.; Kuwajima, T.; Oakley, D.; Nikulina, E.; Hou, J.; Yang, W.S.; Lowry, E.R.; Lamas, N.J.; Amoroso, M.W.; Croft, G.F.; Hosur, R.; Wichterle, H.; Sebti, S.; Filbin, M.T.; Stockwell, B.; Henderson, C.E. Protein prenylation constitutes an endogenous brake on axonal growth. Cell Reports, 2016, 16(2), 545-558. [].
Jin, Y.; Sui, H.J.; Dong, Y.; Ding, Q.; Qu, W.H.; Yu, S.X.; Jin, Y.X. Atorvastatin enhances neurite outgrowth in cortical neurons in vitro via up-regulating the Akt/mTOR and Akt/GSK-3beta signaling pathways. Acta Pharmacol. Sin., 2012, 33(7), 861-872. [http://].
Pooler, A.M.; Xi, S.C.; Wurtman, R.J. The 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitor pravastatin enhances neurite outgrowth in hippocampal neurons. J. Neurochem., 2006, 97(3), 716-723. [ 03763.x].
Gouveia, T.L.; Scorza, F.A.; Iha, H.A.; Frangiotti, M.I.; Perosa, S.R.; Cavalheiro, E.A.; Silva, J.A., Jr; Feliciano, R.S.; de Almeida, A.C.; Naffah-Mazzacoratti, M.G. Lovastatin decreases the synthesis of inflammatory mediators during epileptogenesis in the hippocampus of rats submitted to pilocarpine-induced epilepsy. Epilepsy Behav., 2014, 36, 68-73. [ 04.009].
Griffin, J.M.; Kho, D.; Graham, E.S.; Nicholson, L.F.; O’Carroll, S.J. Statins inhibit fibrillary beta-amyloid induced inflammation in a Model of the human blood brain barrier. PLoS One, 2016, 11(6), e0157483. [].
Reis, P.A.; Alexandre, P.C.; D’Avila, J.C.; Siqueira, L.D.; Antunes, B.; Estato, V.; Tibirica, E.V.; Verdonk, F.; Sharshar, T.; Chretien, F.; Castro-Faria-Neto, H.C.; Bozza, F.A. Statins prevent cognitive impairment after sepsis by reverting neuroinflammation, and microcirculatory/endothelial dysfunction. Brain Behav. Immun., 2017, 60, 293-303. [].
Lim, S.W.; Shiue, Y.L.; Liao, J.C.; Wee, H.Y.; Wang, C.C.; Chio, C.C.; Chang, C.H.; Hu, C.Y.; Kuo, J.R. Simvastatin therapy in the acute stage of traumatic brain injury attenuates brain trauma-induced depression-Like behavior in rats by reducing neuroinflammation in the Hippocampus. Neurocrit. Care, 2017, 26(1), 122-132. [].
Chu, L.W.; Chen, J.Y.; Wu, P.C.; Wu, B.N. Atorvastatin prevents neuroinflammation in chronic constriction injury rats through nuclear NFkappaB downregulation in the dorsal root ganglion and spinal cord. ACS Chem. Neurosci., 2015, 6(6), 889-898. [http://dx.].
Yan, J.; Sun, J.; Huang, L.; Fu, Q.; Du, G. Simvastatin prevents neuroinflammation by inhibiting N-methyl-D-aspartic acid receptor 1 in 6-hydroxydopamine-treated PC12 cells. J. Neurosci. Res., 2014, 92(5), 634-640. [].
Ma, M.W.; Wang, J.; Zhang, Q.; Wang, R.; Dhandapani, K.M.; Vadlamudi, R.K.; Brann, D.W. NADPH oxidase in brain injury and neurodegenerative disorders. Mol. Neurodegener., 2017, 12(1), 7. [].
Kwok, J.M.; Ma, C.C.; Ma, S. Recent development in the effects of statins on cardiovascular disease through Rac1 and NADPH oxidase. Vascul. Pharmacol., 2013, 58(1-2), 21-30. [ 10.1016/j.vph.2012.10.003].
Barone, E.; Cenini, G.; Di Domenico, F.; Martin, S.; Sultana, R.; Mancuso, C.; Murphy, M.P.; Head, E.; Butterfield, D.A. Long-term high-dose atorvastatin decreases brain oxidative and nitrosative stress in a preclinical model of Alzheimer disease: a novel mechanism of action. Pharmacol. Res., 2011, 63(3), 172-180. [http://].
Catalao, C.H.; Santos-Junior, N.N.; da Costa, L.H.; Souza, A.O.; Alberici, L.C.; Rocha, M.J. Brain oxidative stress during experimental sepsis is attenuated by simvastatin administration. Mol. Neurobiol., 2017, 54(9), 7008-7018.
Butterfield, D.A.; Barone, E.; Di Domenico, F.; Cenini, G.; Sultana, R.; Murphy, M.P.; Mancuso, C.; Head, E. Atorvastatin treatment in a dog preclinical model of Alzheimer’s disease leads to up-regulation of haem oxygenase-1 and is associated with reduced oxidative stress in brain. Int. J. Neuropsychopharmacol., 2012, 15(7), 981-987. [].
Tong, X.K.; Nicolakakis, N.; Fernandes, P.; Ongali, B.; Brouillette, J.; Quirion, R.; Hamel, E. Simvastatin improves cerebrovascular function and counters soluble amyloid-beta, inflammation and oxidative stress in aged APP mice. Neurobiol. Dis., 2009, 35(3), 406-414. [].
Hayashi, T.; Hamakawa, K.; Nagotani, S.; Jin, G.; Li, F.; Deguchi, K.; Sehara, Y.; Zhang, H.; Nagano, I.; Shoji, M.; Abe, K. HMG CoA reductase inhibitors reduce ischemic brain injury of Wistar rats through decreasing oxidative stress on neurons. Brain Res., 2005, 1037(1-2), 52-58. [ 12.051].
Simons, K.; Ehehalt, R. Cholesterol, lipid rafts, and disease. J. Clin. Invest., 2002, 110(5), 597-603. [ JCI0216390].
Linetti, A.; Fratangeli, A.; Taverna, E.; Valnegri, P.; Francolini, M.; Cappello, V.; Matteoli, M.; Passafaro, M.; Rosa, P. Cholesterol reduction impairs exocytosis of synaptic vesicles. J. Cell Sci., 2010, 123(Pt 4), 595-605. [].
Pani, A.; Mandas, A.; Dessi, S. Cholesterol, Alzheimer’s disease, prion disorders: a menage a trois? Curr. Drug Targets, 2010, 11(8), 1018-1031. [].
Karasinska, J.M.; Hayden, M.R. Cholesterol metabolism in Huntington disease. Nat. Rev. Neurol., 2011, 7(10), 561-572. [].
Porter, F.D.; Herman, G.E. Malformation syndromes caused by disorders of cholesterol synthesis. J. Lipid Res., 2011, 52(1), 6-34. [].
Tint, G.S.; Irons, M.; Elias, E.R.; Batta, A.K.; Frieden, R.; Chen, T.S.; Salen, G. Defective cholesterol biosynthesis associated with the Smith-Lemli-Opitz syndrome. N. Engl. J. Med., 1994, 330(2), 107-113. [].
Nowaczyk, M.J.; Zeesman, S.; Waye, J.S.; Douketis, J.D. Incidence of Smith-Lemli-Opitz syndrome in Canada: results of three-year population surveillance. J. Pediatr., 2004, 145(4), 530-535. [].
Vance, J.E. Dysregulation of cholesterol balance in the brain: contribution to neurodegenerative diseases. Dis. Model. Mech., 2012, 5(6), 746-755. [].
Chan, Y.M.; Merkens, L.S.; Connor, W.E.; Roullet, J.B.; Penfield, J.A.; Jordan, J.M.; Steiner, R.D.; Jones, P.J. Effects of dietary cholesterol and simvastatin on cholesterol synthesis in Smith-Lemli-Opitz syndrome. Pediatr. Res., 2009, 65(6), 681-685. [].
Porter, F.D. Human malformation syndromes due to inborn errors of cholesterol synthesis. Curr. Opin. Pediatr., 2003, 15(6), 607-613. [].
Elias, E.R.; Irons, M.B.; Hurley, A.D.; Tint, G.S.; Salen, G. Clinical effects of cholesterol supplementation in six patients with the Smith-Lemli-Opitz syndrome (SLOS). Am. J. Med. Genet., 1997, 68(3), 305-310. [ 68:3<305:AID-AJMG11>3.0.CO;2-X].
Linck, L.M.; Lin, D.S.; Flavell, D.; Connor, W.E.; Steiner, R.D. Cholesterol supplementation with egg yolk increases plasma cholesterol and decreases plasma 7-dehydrocholesterol in Smith-Lemli-Opitz syndrome. Am. J. Med. Genet., 2000, 93(5), 360-365. [<360:AID-AJMG4>3.0.CO;2-P].
Pappu, A.S.; Steiner, R.D.; Connor, S.L.; Flavell, D.P.; Lin, D.S.; Hatcher, L.; Illingworth, D.R.; Connor, W.E. Feedback inhibition of the cholesterol biosynthetic pathway in patients with Smith-Lemli-Opitz syndrome as demonstrated by urinary mevalonate excretion. J. Lipid Res., 2002, 43(10), 1661-1669. [ 10.1194/jlr.M200163-JLR200].
Merkens, L.S.; Connor, W.E.; Linck, L.M.; Lin, D.S.; Flavell, D.P.; Steiner, R.D. Effects of dietary cholesterol on plasma lipoproteins in smith-Lemli-Opitz syndrome. Pediatr. Res., 2004, 56(5), 726-732. [].
Dietschy, J.M.; Turley, S.D. Cholesterol metabolism in the brain. Curr. Opin. Lipidol., 2001, 12(2), 105-112. [ 10.1097/00041433-200104000-00003].
Wassif, C.A.; Krakowiak, P.A.; Wright, B.S.; Gewandter, J.S.; Sterner, A.L.; Javitt, N.; Yergey, A.L.; Porter, F.D. Residual cholesterol synthesis and simvastatin induction of cholesterol synthesis in Smith-Lemli-Opitz syndrome fibroblasts. Mol. Genet. Metab., 2005, 85(2), 96-107. [ 009].
Correa-Cerro, L.S.; Wassif, C.A.; Kratz, L.; Miller, G.F.; Munasinghe, J.P.; Grinberg, A.; Fliesler, S.J.; Porter, F.D. Development and characterization of a hypomorphic Smith-Lemli-Opitz syndrome mouse model and efficacy of simvastatin therapy. Hum. Mol. Genet., 2006, 15(6), 839-851. [ ddl003].
Haas, D.; Garbade, S.F.; Vohwinkel, C.; Muschol, N.; Trefz, F.K.; Penzien, J.M.; Zschocke, J.; Hoffmann, G.F.; Burgard, P. Effects of cholesterol and simvastatin treatment in patients with Smith-Lemli-Opitz syndrome (SLOS). J. Inherit. Metab. Dis., 2007, 30(3), 375-387. [].
Jira, P.E.; Wevers, R.A.; de Jong, J.; Rubio-Gozalbo, E.; Janssen-Zijlstra, F.S.; van Heyst, A.F.; Sengers, R.C.; Smeitink, J.A. Simvastatin. A new therapeutic approach for Smith-Lemli-Opitz syndrome. J. Lipid Res., 2000, 41(8), 1339-1346.
Peprah, E. Fragile X syndrome: the FMR1 CGG repeat distribution among world populations. Ann. Hum. Genet., 2012, 76(2), 178-191. [].
Gallagher, A.; Hallahan, B. Fragile X-associated disorders: a clinical overview. J. Neurol., 2012, 259(3), 401-413. [ 10.1007/s00415-011-6161-3].
Hessl, D.; Nguyen, D.V.; Green, C.; Chavez, A.; Tassone, F.; Hagerman, R.J.; Senturk, D.; Schneider, A.; Lightbody, A.; Reiss, A.L.; Hall, S. A solution to limitations of cognitive testing in children with intellectual disabilities: the case of fragile X syndrome. J. Neurodev. Disord., 2009, 1(1), 33-45. [ s11689-008-9001-8].
Wadell, P.M.; Hagerman, R.J.; Hessl, D.R.; Fragile, X. Syndrome: Psychiatric Manifestations, Assessment and Emerging Therapies. Curr. Psychiatry Rev., 2013, 9(1), 53-58.
Verkerk, A.J.; Pieretti, M.; Sutcliffe, J.S.; Fu, Y.H.; Kuhl, D.P.; Pizzuti, A.; Reiner, O.; Richards, S.; Victoria, M.F.; Zhang, F.P. Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell, 1991, 65(5), 905-914. [ 10.1016/0092-8674(91)90397-H].
Corbin, F.; Bouillon, M.; Fortin, A.; Morin, S.; Rousseau, F.; Khandjian, E.W. The fragile X mental retardation protein is associated with poly(A)+ mRNA in actively translating polyribosomes. Hum. Mol. Genet., 1997, 6(9), 1465-1472. [ 1093/hmg/6.9.1465].
Irwin, S.A.; Patel, B.; Idupulapati, M.; Harris, J.B.; Crisostomo, R.A.; Larsen, B.P.; Kooy, F.; Willems, P.J.; Cras, P.; Kozlowski, P.B.; Swain, R.A.; Weiler, I.J.; Greenough, W.T. Abnormal dendritic spine characteristics in the temporal and visual cortices of patients with fragile-X syndrome: a quantitative examination. Am. J. Med. Genet., 2001, 98(2), 161-167. [ 1096-8628(20010115)98:2<161:AID-AJMG1025>3.0.CO;2-B].
Bhakar, A.L.; Dolen, G.; Bear, M.F. The pathophysiology of fragile X (and what it teaches us about synapses). Annu. Rev. Neurosci., 2012, 35, 417-443. [].
Hou, L.; Antion, M.D.; Hu, D.; Spencer, C.M.; Paylor, R.; Klann, E. Dynamic translational and proteasomal regulation of fragile X mental retardation protein controls mGluR-dependent long-term depression. Neuron, 2006, 51(4), 441-454. [ 1016/j.neuron.2006.07.005].
Price, T.J.; Rashid, M.H.; Millecamps, M.; Sanoja, R.; Entrena, J.M.; Cervero, F. Decreased nociceptive sensitization in mice lacking the fragile X mental retardation protein: role of mGluR1/5 and mTOR. J. Neurosci., 2007, 27(51), 13958-13967. [http://dx.doi. org/10.1523/JNEUROSCI.4383-07.2007].
Osterweil, E.K.; Krueger, D.D.; Reinhold, K.; Bear, M.F. Hypersensitivity to mGluR5 and ERK1/2 leads to excessive protein synthesis in the hippocampus of a mouse model of fragile X syndrome. J. Neurosci., 2010, 30(46), 15616-15627. [ 1523/JNEUROSCI.3888-10.2010].
Cerezo-Guisado, M.I.; Garcia-Roman, N.; Garcia-Marin, L.J.; Alvarez-Barrientos, A.; Bragado, M.J.; Lorenzo, M.J. Lovastatin inhibits the extracellular-signal-regulated kinase pathway in immortalized rat brain neuroblasts. Biochem. J., 2007, 401(1), 175-183. [].
Kumari, R.; Castillo, C.; Francesconi, A. Agonist-dependent signaling by group I metabotropic glutamate receptors is regulated by association with lipid domains. J. Biol. Chem., 2013, 288(44), 32004-32019. [].
Osterweil, E.K.; Chuang, S.C.; Chubykin, A.A.; Sidorov, M.; Bianchi, R.; Wong, R.K.; Bear, M.F. Lovastatin corrects excess protein synthesis and prevents epileptogenesis in a mouse model of fragile X syndrome. Neuron, 2013, 77(2), 243-250. [http://dx.doi. org/10.1016/j.neuron.2012.01.034].
Li, W.; Cui, Y.; Kushner, S.A.; Brown, R.A.; Jentsch, J.D.; Frankland, P.W.; Cannon, T.D.; Silva, A.J. The HMG-CoA reductase inhibitor lovastatin reverses the learning and attention deficits in a mouse model of neurofibromatosis type 1. Curr. Biol., 2005, 15(21), 1961-1967. [].
Caku, A.; Pellerin, D.; Bouvier, P.; Riou, E.; Corbin, F. Effect of lovastatin on behavior in children and adults with fragile X syndrome: an open-label study. Am. J. Med. Genet. A., 2014, 164A(11), 2834-2842. [].
Bailey, D.B., Jr; Raspa, M.; Bishop, E.; Olmsted, M.; Mallya, U.G.; Berry-Kravis, E. Medication utilization for targeted symptoms in children and adults with fragile X syndrome: US survey. J. Dev. Behav. Pediatr., 2012, 33(1), 62-69. [ 1097/DBP.0b013e318236c0e1].
Patankar, J.V. Cholesterol metabolism is a potential therapeutic target for Rett syndrome. Clin. Genet., 2014, 85(3), 229-230. [].
Chahrour, M.; Jung, S.Y.; Shaw, C.; Zhou, X.; Wong, S.T.; Qin, J.; Zoghbi, H.Y. MeCP2, a key contributor to neurological disease, activates and represses transcription. Science, 2008, 320(5880), 1224-1229. [].
Amir, R.E.; Van den Veyver, I.B.; Wan, M.; Tran, C.Q.; Francke, U.; Zoghbi, H.Y. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat. Genet., 1999, 23(2), 185-188. [].
Macdonald, J.L.; Verster, A.; Berndt, A.; Roskams, A.J. MBD2 and MeCP2 regulate distinct transitions in the stage-specific differentiation of olfactory receptor neurons. Mol. Cell. Neurosci., 2010, 44(1), 55-67. [].
Villani, C.; Sacchetti, G.; Bagnati, R.; Passoni, A.; Fusco, F.; Carli, M.; Invernizzi, R.W. Lovastatin fails to improve motor performance and survival in methyl-CpG-binding protein2-null mice. eLife, 2018, 5, 1-14.
Zoghbi, H.Y.; Bear, M.F. Synaptic dysfunction in neurodevelopmental disorders associated with autism and intellectual disabilities. Cold Spring Harb. Perspect. Biol., 2012, 4(3) [http://dx.doi. org/10.1101/cshperspect.a009886].
Huguet, G.; Ey, E.; Bourgeron, T. The genetic landscapes of autism spectrum disorders. Annu. Rev. Genomics Hum. Genet., 2013, 14, 191-213. [].
Vargas, D.L.; Nascimbene, C.; Krishnan, C.; Zimmerman, A.W.; Pardo, C.A. Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann. Neurol., 2005, 57(1), 67-81. [].
Molloy, C.A.; Morrow, A.L.; Meinzen-Derr, J.; Schleifer, K.; Dienger, K.; Manning-Courtney, P.; Altaye, M.; Wills-Karp, M. Elevated cytokine levels in children with autism spectrum disorder. J. Neuroimmunol., 2006, 172(1-2), 198-205. [ 1016/j.jneuroim.2005.11.007].
Lee, J.K.; Won, J.S.; Singh, A.K.; Singh, I. Statin inhibits kainic acid-induced seizure and associated inflammation and hippocampal cell death. Neurosci. Lett., 2008, 440(3), 260-264. [http://dx.doi. org/10.1016/j.neulet.2008.05.112].
Ramirez, C.; Tercero, I.; Pineda, A.; Burgos, J.S. Simvastatin is the statin that most efficiently protects against kainate-induced excitotoxicity and memory impairment. J. Alzheimers Dis., 2011, 24(1), 161-174. [].
Xie, C.; Sun, J.; Qiao, W.; Lu, D.; Wei, L.; Na, M.; Song, Y.; Hou, X.; Lin, Z. Administration of simvastatin after kainic acid-induced status epilepticus restrains chronic temporal lobe epilepsy. PLoS One, 2011, 6(9), e24966. [ 0024966].
van Vliet, E.A.; Holtman, L.; Aronica, E.; Schmitz, L.J.; Wadman, W.J.; Gorter, J.A. Atorvastatin treatment during epileptogenesis in a rat model for temporal lobe epilepsy. Epilepsia, 2011, 52(7), 1319-1330. [].
Serbanescu, I.; Ryan, M.A.; Shukla, R.; Cortez, M.A.; Snead, O.C., III; Cunnane, S.C. Lovastatin exacerbates atypical absence seizures with only minimal effects on brain sterols. J. Lipid Res., 2004, 45(11), 2038-2043. [].
Canitano, R. Epilepsy in autism spectrum disorders. Eur. Child Adolesc. Psychiatry, 2007, 16(1), 61-66. [ 1007/s00787-006-0563-2].
Pintaudi, M.; Calevo, M.G.; Vignoli, A.; Parodi, E.; Aiello, F.; Baglietto, M.G.; Hayek, Y.; Buoni, S.; Renieri, A.; Russo, S.; Cogliati, F.; Giordano, L.; Canevini, M.; Veneselli, E. Epilepsy in Rett syndrome: clinical and genetic features. Epilepsy Behav., 2010, 19(3), 296-300. [].
Querfurth, H.W.; LaFerla, F.M. Alzheimer’s disease. N. Engl. J. Med., 2010, 362(4), 329-344. [ 0909142].
Bonda, D.J.; Wang, X.; Lee, H.G.; Smith, M.A.; Perry, G.; Zhu, X. Neuronal failure in Alzheimer’s disease: a view through the oxidative stress looking-glass. Neurosci. Bull., 2014, 30(2), 243-252. [].
Alzheimer, A. Uber eine eigenartige Erkrankung der Hirnrinde. Allgemeine Zeitschrife Psychiatrie, 1907, 64, 146-148.
Wood, W.G.; Igbavboa, U.; Eckert, G.P.; Johnson-Anuna, L.N.; Muller, W.E. Is hypercholesterolemia a risk factor for Alzheimer’s disease? Mol. Neurobiol., 2005, 31(1-3), 185-192. [http://dx.doi. org/10.1385/MN:31:1-3:185].
Yu, J.T.; Tan, L.; Hardy, J. Apolipoprotein E in Alzheimer’s disease: an update. Annu. Rev. Neurosci., 2014, 37, 79-100. [].
Liu, C.C.; Kanekiyo, T.; Xu, H.; Bu, G. Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy. Nat. Rev. Neurol., 2013, 9(2), 106-118. [].
Christensen, D.Z.; Schneider-Axmann, T.; Lucassen, P.J.; Bayer, T.A.; Wirths, O. Accumulation of intraneuronal Abeta correlates with ApoE4 genotype. Acta Neuropathol., 2010, 119(5), 555-566. [].
Hashimoto, T.; Serrano-Pozo, A.; Hori, Y.; Adams, K.W.; Takeda, S.; Banerji, A.O.; Mitani, A.; Joyner, D.; Thyssen, D.H.; Bacskai, B.J.; Frosch, M.P.; Spires-Jones, T.L.; Finn, M.B.; Holtzman, D.M.; Hyman, B.T. Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid beta peptide. J. Neurosci., 2012, 32(43), 15181-15192. [ JNEUROSCI.1542-12.2012].
Koffie, R.M.; Hashimoto, T.; Tai, H.C.; Kay, K.R.; Serrano-Pozo, A.; Joyner, D.; Hou, S.; Kopeikina, K.J.; Frosch, M.P.; Lee, V.M.
Holtzman, D.M.; Hyman, B.T.; Spires-Jones, T.L. Apolipoprotein E4 effects in Alzheimer’s disease are mediated by synaptotoxic oligomeric amyloid-beta. Brain, 2012, 135(Pt 7), 2155-2168. [].
Bu, G. Apolipoprotein E and its receptors in Alzheimer’s disease: pathways, pathogenesis and therapy. Nat. Rev. Neurosci., 2009, 10(5), 333-344. [].
Hottman, D.A.; Li, L. Protein prenylation and synaptic plasticity: implications for Alzheimer’s disease. Mol. Neurobiol., 2014, 50(1), 177-185. [].
Pedrini, S.; Carter, T.L.; Prendergast, G.; Petanceska, S.; Ehrlich, M.E.; Gandy, S. Modulation of statin-activated shedding of Alzheimer APP ectodomain by ROCK. PLoS Med., 2005, 2(1), e18. [].
Cole, S.L.; Grudzien, A.; Manhart, I.O.; Kelly, B.L.; Oakley, H.; Vassar, R. Statins cause intracellular accumulation of amyloid precursor protein, beta-secretase-cleaved fragments, and amyloid beta-peptide via an isoprenoid-dependent mechanism. J. Biol. Chem., 2005, 280(19), 18755-18770. [ jbc.M413895200].
Ostrowski, S.M.; Wilkinson, B.L.; Golde, T.E.; Landreth, G. Statins reduce amyloid-beta production through inhibition of protein isoprenylation. J. Biol. Chem., 2007, 282(37), 26832-26844. [].
Simons, M.; Schwarzler, F.; Lutjohann, D.; von Bergmann, K.; Beyreuther, K.; Dichgans, J.; Wormstall, H.; Hartmann, T.; Schulz, J.B. Treatment with simvastatin in normocholesterolemic patients with Alzheimer’s disease: A 26-week randomized, placebo-controlled, double-blind trial. Ann. Neurol., 2002, 52(3), 346-350. [].
Fassbender, K.; Simons, M.; Bergmann, C.; Stroick, M.; Lutjohann, D.; Keller, P.; Runz, H.; Kuhl, S.; Bertsch, T.; von Bergmann, K.; Hennerici, M.; Beyreuther, K.; Hartmann, T. Simvastatin strongly reduces levels of Alzheimer’s disease beta -amyloid peptides Abeta 42 and Abeta 40 in vitro and in vivo. Proc. Natl. Acad. Sci. USA, 2001, 98(10), 5856-5861. [ pnas.081620098].
Tamboli, I.Y.; Barth, E.; Christian, L.; Siepmann, M.; Kumar, S.; Singh, S.; Tolksdorf, K.; Heneka, M.T.; Lutjohann, D.; Wunderlich, P.; Walter, J. Statins promote the degradation of extracellular amyloid beta-peptide by microglia via stimulation of exosome-associated insulin-degrading enzyme (IDE) secretion. J. Biol. Chem., 2010, 285(48), 37405-37414. [ jbc.M110.149468].
Kurata, T.; Miyazaki, K.; Kozuki, M.; Panin, V.L.; Morimoto, N.; Ohta, Y.; Nagai, M.; Ikeda, Y.; Matsuura, T.; Abe, K. Atorvastatin and pitavastatin improve cognitive function and reduce senile plaque and phosphorylated tau in aged APP mice. Brain Res., 2011, 1371, 161-170. [].
Murphy, M.P.; Morales, J.; Beckett, T.L.; Astarita, G.; Piomelli, D.; Weidner, A.; Studzinski, C.M.; Dowling, A.L.; Wang, X.; Levine, H., III; Kryscio, R.J.; Lin, Y.; Barrett, E.; Head, E. Changes in cognition and amyloid-beta processing with long term cholesterol reduction using atorvastatin in aged dogs. J. Alzheimers Dis., 2010, 22(1), 135-150. [].
SjÃgren, M.; Blennow, K. The link between cholesterol and Alzheimer’s disease. World J. Biol. Psychiatry, 2005, 6(2), 85-97. [].
Salins, P.; Shawesh, S.; He, Y.; Dibrov, A.; Kashour, T.; Arthur, G.; Amara, F. Lovastatin protects human neurons against Abeta-induced toxicity and causes activation of beta-catenin-TCF/LEF signaling. Neurosci. Lett., 2007, 412(3), 211-216. [http://dx.doi. org/10.1016/j.neulet.2006.07.045].
Kurata, T.; Miyazaki, K.; Morimoto, N.; Kawai, H.; Ohta, Y.; Ikeda, Y.; Abe, K. Atorvastatin and pitavastatin reduce oxidative stress and improve IR/LDL-R signals in Alzheimer’s disease. Neurol. Res., 2013, 35(2), 193-205. [ 1743132812Y.0000000127].
Zhang, Y.Y.; Fan, Y.C.; Wang, M.; Wang, D.; Li, X.H. Atorvastatin attenuates the production of IL-1beta, IL-6, and TNF-alpha in the hippocampus of an amyloid beta1-42-induced rat model of Alzheimer’s disease. Clin. Interv. Aging, 2013, 8, 103-110.
Hoglund, K.; Thelen, K.M.; Syversen, S.; Sjogren, M.; von Bergmann, K.; Wallin, A.; Vanmechelen, E.; Vanderstichele, H.; Lutjohann, D.; Blennow, K. The effect of simvastatin treatment on the amyloid precursor protein and brain cholesterol metabolism in patients with Alzheimer’s disease. Dement. Geriatr. Cogn. Disord., 2005, 19(5-6), 256-265. [].
Malfitano, A.M.; Marasco, G.; Proto, M.C.; Laezza, C.; Gazzerro, P.; Bifulco, M. Statins in neurological disorders: an overview and update. Pharmacol. Res., 2014, 88, 74-83. [ 1016/j.phrs.2014.06.007].
Li, G.; Higdon, R.; Kukull, W.A.; Peskind, E.; Van Valen Moore, K.; Tsuang, D.; van Belle, G.; McCormick, W.; Bowen, J.D.; Teri, L.; Schellenberg, G.D.; Larson, E.B. Statin therapy and risk of dementia in the elderly: a community-based prospective cohort study. Neurology, 2004, 63(9), 1624-1628. [ 01.WNL.0000142963.90204.58].
Sparks, D.L.; Sabbagh, M.N.; Connor, D.J.; Lopez, J.; Launer, L.J.; Browne, P.; Wasser, D.; Johnson-Traver, S.; Lochhead, J.; Ziolwolski, C. Atorvastatin for the treatment of mild to moderate Alzheimer disease: preliminary results. Arch. Neurol., 2005, 62(5), 753-757. [].
Dufouil, C.; Richard, F.; Fievet, N.; Dartigues, J.F.; Ritchie, K.; Tzourio, C.; Amouyel, P.; Alperovitch, A. APOE genotype, cholesterol level, lipid-lowering treatment, and dementia: the Three-City Study. Neurology, 2005, 64(9), 1531-1538. [ 1212/01.WNL.0000160114.42643.31].
Sparks, D.L.; Kryscio, R.J.; Sabbagh, M.N.; Connor, D.J.; Sparks, L.M.; Liebsack, C. Reduced risk of incident AD with elective statin use in a clinical trial cohort. Curr. Alzheimer Res., 2008, 5(4), 416-421. [].
Li, G.; Shofer, J.B.; Rhew, I.C.; Kukull, W.A.; Peskind, E.R.; McCormick, W.; Bowen, J.D.; Schellenberg, G.D.; Crane, P.K.; Breitner, J.C.; Larson, E.B. Age-varying association between statin use and incident Alzheimer’s disease. J. Am. Geriatr. Soc., 2010, 58(7), 1311-1317. [ 02906.x].
Mendoza-Oliva, A.; Zepeda, A.; Arias, C. The complex actions of statins in brain and their relevance for Alzheimer’s disease treatment: an analytical review. Curr. Alzheimer Res., 2014, 11(9), 817-833.
Fan, Q.W.; Yu, W.; Senda, T.; Yanagisawa, K.; Michikawa, M. Cholesterol-dependent modulation of tau phosphorylation in cultured neurons. J. Neurochem., 2001, 76(2), 391-400. [http://dx.doi. org/10.1046/j.1471-4159.2001.00063.x].
Mendoza-Oliva, A.; Ferrera, P.; Arias, C. Interplay Between Cholesterol and Homocysteine in the Exacerbation of Amyloid-beta Toxicity in Human Neuroblastoma Cells. CNS Neurol. Disord. Drug Targets, 2013. [ 90083].
Marcuzzi, A.; Tricarico, P.M.; Piscianz, E.; Kleiner, G.; Vecchi Brumatti, L.; Crovella, S. Lovastatin induces apoptosis through the mitochondrial pathway in an undifferentiated SH-SY5Y neuroblastoma cell line. Cell Death Dis., 2013, 4, e585. [ 10.1038/cddis.2013.112].
Saeed, U.; Compagnone, J.; Aviv, R.I.; Strafella, A.P.; Black, S.E.; Lang, A.E.; Masellis, M. Imaging biomarkers in Parkinson’s disease and Parkinsonian syndromes: current and emerging concepts. Transl. Neurodegener., 2017, 6, 8. [].
Kalia, L.V.; Lang, A.E. Parkinson’s disease. Lancet, 2015, 386(9996), 896-912. [ 61393-3].
Bai, S.; Song, Y.; Huang, X.; Peng, L.; Jia, J.; Liu, Y.; Lu, H. Statin use and the risk of parkinson’s disease: An updated meta-analysis. PLoS One, 2016, 11(3), e0152564. [ pone.0152564].
Corti, O.; Lesage, S.; Brice, A. What genetics tells us about the causes and mechanisms of Parkinson’s disease. Physiol. Rev., 2011, 91(4), 1161-1218. [ 2010].
Giannoccaro, M.P.; La Morgia, C.; Rizzo, G.; Carelli, V. Mitochondrial DNA and primary mitochondrial dysfunction in Parkinson’s disease. Mov. Disord., 2017, 32(3), 346-363. [http://dx.doi. org/10.1002/mds.26966].
Ng, C.H.; Guan, M.S.; Koh, C.; Ouyang, X.; Yu, F.; Tan, E.K.; O’Neill, S.P.; Zhang, X.; Chung, J.; Lim, K.L. AMP kinase activation mitigates dopaminergic dysfunction and mitochondrial abnormalities in Drosophila models of Parkinson’s disease. J. Neurosci., 2012, 32(41), 14311-14317. [ 0499-12.2012].
Cheung, Z.H.; Ip, N.Y. The emerging role of autophagy in Parkinson’s disease. Mol. Brain, 2009, 2, 29. [ 1756-6606-2-29].
Levine, B. Eating oneself and uninvited guests: autophagy-related pathways in cellular defense. Cell, 2005, 120(2), 159-162.
Glick, D.; Barth, S.; Macleod, K.F. Autophagy: cellular and molecular mechanisms. J. Pathol., 2010, 221(1), 3-12. [http://dx.].
Lynch-Day, M.A.; Mao, K.; Wang, K.; Zhao, M.; Klionsky, D.J. The role of autophagy in Parkinson’s disease. Cold Spring Harb. Perspect. Med., 2012, 2(4), a009357. [ cshperspect.a009357].
Li, Q.; Zhuang, Q.K.; Yang, J.N.; Zhang, Y.Y. Statins excert neuroprotection on cerebral ischemia independent of their lipid-lowering action: the potential molecular mechanisms. Eur. Rev. Med. Pharmacol. Sci., 2014, 18(8), 1113-1126.
Kang, S.Y.; Lee, S.B.; Kim, H.J.; Kim, H.T.; Yang, H.O.; Jang, W. Autophagic modulation by rosuvastatin prevents rotenone-induced neurotoxicity in an in vitro model of Parkinson’s disease. Neurosci. Lett., 2017, 642, 20-26. [ 063].
Gao, X.; Simon, K.C.; Schwarzschild, M.A.; Ascherio, A. Prospective study of statin use and risk of Parkinson disease. Arch. Neurol., 2012, 69(3), 380-384. [ 1060].
Illingworth, D.R.; Crouse, J.R., III; Hunninghake, D.B.; Davidson, M.H.; Escobar, I.D.; Stalenhoef, A.F.; Paragh, G.; Ma, P.T.; Liu, M.; Melino, M.R.; O’Grady, L.; Mercuri, M.; Mitchel, Y.B. A comparison of simvastatin and atorvastatin up to maximal recommended doses in a large multicenter randomized clinical trial. Curr. Med. Res. Opin., 2001, 17(1), 43-50. [ 0300799039117026].
van der Most, P.J.; Dolga, A.M.; Nijholt, I.M.; Luiten, P.G.; Eisel, U.L. Statins: mechanisms of neuroprotection. Prog. Neurobiol., 2009, 88(1), 64-75. [ 002].
Sierra, S.; Ramos, M.C.; Molina, P.; Esteo, C.; Vazquez, J.A.; Burgos, J.S. Statins as neuroprotectants: a comparative in vitro study of lipophilicity, blood-brain-barrier penetration, lowering of brain cholesterol, and decrease of neuron cell death. J. Alzheimers Dis., 2011, 23(2), 307-318. [].
Wolozin, B.; Wang, S.W.; Li, N.C.; Lee, A.; Lee, T.A.; Kazis, L.E. Simvastatin is associated with a reduced incidence of dementia and Parkinson’s disease. BMC Med., 2007, 5, 20. [ 1186/1741-7015-5-20].
Huang, X.; Alonso, A.; Guo, X.; Umbach, D.M.; Lichtenstein, M.L.; Ballantyne, C.M.; Mailman, R.B.; Mosley, T.H.; Chen, H. Statins, plasma cholesterol, and risk of Parkinson’s disease: a prospective study. Mov. Disord., 2015, 30(4), 552-559. [http://dx.doi. org/10.1002/mds.26152].
Valenza, M.; Cattaneo, E. Emerging roles for cholesterol in Huntington’s disease. Trends Neurosci., 2011, 34(9), 474-486. [].
Chen, J.Y.; Tran, C.; Hwang, L.; Deng, G.; Jung, M.E.; Faull, K.F.; Levine, M.S.; Cepeda, C. Partial Amelioration of Peripheral and Central Symptoms of Huntington’s Disease via Modulation of Lipid Metabolism. J. Huntingtons Dis., 2016, 5(1), 65-81. [http://].
Valenza, M.; Leoni, V.; Karasinska, J.M.; Petricca, L.; Fan, J.; Carroll, J.; Pouladi, M.A.; Fossale, E.; Nguyen, H.P.; Riess, O.; MacDonald, M.; Wellington, C.; DiDonato, S.; Hayden, M.; Cattaneo, E. Cholesterol defect is marked across multiple rodent models of Huntington’s disease and is manifest in astrocytes. J. Neurosci., 2010, 30(32), 10844-10850. [ 0917-10.2010].
Valenza, M.; Marullo, M.; Di Paolo, E.; Cesana, E.; Zuccato, C.; Biella, G.; Cattaneo, E. Disruption of astrocyte-neuron cholesterol cross talk affects neuronal function in Huntington’s disease. Cell Death Differ., 2015, 22(4), 690-702. [ 2014.162].
Shankaran, M.; Di Paolo, E.; Leoni, V.; Caccia, C.; Ferrari Bardile, C.; Mohammed, H.; Di Donato, S.; Kwak, S.; Marchionini, D.; Turner, S.; Cattaneo, E.; Valenza, M. Early and brain region-specific decrease of de novo cholesterol biosynthesis in Huntington’s disease: A cross-validation study in Q175 knock-in mice. Neurobiol. Dis., 2017, 98, 66-76. [ j.nbd.2016.11.013].
Valenza, M.; Leoni, V.; Tarditi, A.; Mariotti, C.; Bjorkhem, I.; Di Donato, S.; Cattaneo, E. Progressive dysfunction of the cholesterol biosynthesis pathway in the R6/2 mouse model of Huntington’s disease. Neurobiol. Dis., 2007, 28(1), 133-142. [http://dx.doi. org/10.1016/j.nbd.2007.07.004].
Trushina, E.; Singh, R.D.; Dyer, R.B.; Cao, S.; Shah, V.H.; Parton, R.G.; Pagano, R.E.; McMurray, C.T. Mutant huntingtin inhibits clathrin-independent endocytosis and causes accumulation of cholesterol in vitro and in vivo. Hum. Mol. Genet., 2006, 15(24), 3578-3591. [].
del Toro, D.; Xifro, X.; Pol, A.; Humbert, S.; Saudou, F.; Canals, J.M.; Alberch, J. Altered cholesterol homeostasis contributes to enhanced excitotoxicity in Huntington’s disease. J. Neurochem., 2010, 115(1), 153-167. [ 2010.06912.x].
Boussicault, L.; Alves, S.; Lamaziere, A.; Planques, A.; Heck, N.; Moumne, L.; Despres, G.; Bolte, S.; Hu, A.; Pages, C.; Galvan, L.; Piguet, F.; Aubourg, P.; Cartier, N.; Caboche, J.; Betuing, S. CYP46A1, the rate-limiting enzyme for cholesterol degradation, is neuroprotective in Huntington’s disease. Brain, 2016, 139(Pt 3), 953-970. [].
Valenza, M.; Cattaneo, E. Cholesterol dysfunction in neurodegenerative diseases: is Huntington’s disease in the list? Prog. Neurobiol., 2006, 80(4), 165-176. [ 2006.09.005].
Burns, M.P.; Igbavboa, U.; Wang, L.; Wood, W.G.; Duff, K. Cholesterol distribution, not total levels, correlate with altered amyloid precursor protein processing in statin-treated mice. Neuromol. Med., 2006, 8(3), 319-328. [].
Hindler, K.; Cleeland, C.S.; Rivera, E.; Collard, C.D. The role of statins in cancer therapy. Oncologist, 2006, 11(3), 306-315. [].
Wejde, J.; Hjertman, M.; Carlberg, M.; Egestad, B.; Griffiths, W.J.; Sjovall, J.; Larsson, O. Dolichol-like lipids with stimulatory effect on DNA synthesis: substrates for protein dolichylation? J. Cell. Biochem., 1998, 71(4), 502-514. [ (SICI)1097-4644(19981215)71:4<502:AID-JCB5>3.0.CO;2-P].
Murtola, T.J.; Visvanathan, K.; Artama, M.; Vainio, H.; Pukkala, E. Statin use and breast cancer survival: a nationwide cohort study from Finland. PLoS One, 2014, 9(10), e110231. [ 10.1371/journal.pone.0110231].
Song, C.; Park, S.; Park, J.; Shim, M.; Kim, A.; Jeong, I.G.; Hong, J.H.; Kim, C.S.; Ahn, H. Statin use after radical prostatectomy reduces biochemical recurrence in men with prostate cancer. Prostate, 2015, 75(2), 211-217. [].
Wei, T.T.; Lin, Y.T.; Chen, W.S.; Luo, P.; Lin, Y.C.; Shun, C.T.; Lin, Y.H.; Chen, J.B.; Chen, N.W.; Fang, J.M.; Wu, M.S.; Yang, K.C.; Chang, L.C.; Tai, K.Y.; Liang, J.T.; Chen, C.C. Dual targeting of 3-Hydroxy-3-methylglutaryl coenzyme a reductase and histone deacetylase as a therapy for colorectal cancer. EBioMedicine, 2016, 10, 124-136. [].
Minden, M.D.; Dimitroulakos, J.; Nohynek, D.; Penn, L.Z. Lovastatin induced control of blast cell growth in an elderly patient with acute myeloblastic leukemia. Leuk. Lymphoma, 2001, 40(5-6), 659-662. [].
Kawata, S.; Yamasaki, E.; Nagase, T.; Inui, Y.; Ito, N.; Matsuda, Y.; Inada, M.; Tamura, S.; Noda, S.; Imai, Y.; Matsuzawa, Y. Effect of pravastatin on survival in patients with advanced hepatocellular carcinoma. A randomized controlled trial. Br. J. Cancer, 2001, 84(7), 886-891. [].
Kim, W.S.; Kim, M.M.; Choi, H.J.; Yoon, S.S.; Lee, M.H.; Park, K.; Park, C.H.; Kang, W.K. Phase II study of high-dose lovastatin in patients with advanced gastric adenocarcinoma. Invest. New Drugs, 2001, 19(1), 81-83. [].
Knox, J.J.; Siu, L.L.; Chen, E.; Dimitroulakos, J.; Kamel-Reid, S.; Moore, M.J.; Chin, S.; Irish, J.; LaFramboise, S.; Oza, A.M. A Phase I trial of prolonged administration of lovastatin in patients with recurrent or metastatic squamous cell carcinoma of the head and neck or of the cervix. Eur. J. Cancer, 2005, 41(4), 523-530. [].
Ohgaki, H. Epidemiology of brain tumors. Methods Mol. Biol., 2009, 472, 323-342. [].
Appin, C.L.; Brat, D.J. Molecular pathways in gliomagenesis and their relevance to neuropathologic diagnosis. Adv. Anat. Pathol., 2015, 22(1), 50-58. [ 48].
Koyuturk, M.; Ersoz, M.; Altiok, N. Simvastatin induces proliferation inhibition and apoptosis in C6 glioma cells via c-jun N-terminal kinase. Neurosci. Lett., 2004, 370(2-3), 212-217. [http://].
Yanae, M.; Tsubaki, M.; Satou, T.; Itoh, T.; Imano, M.; Yamazoe, Y.; Nishida, S. Statin-induced apoptosis via the suppression of ERK1/2 and Akt activation by inhibition of the geranylgeranyl-pyrophosphate biosynthesis in glioblastoma. J. Exp. Clin. Cancer Res., 2011, 30, 74. [].
Jiang, Z.; Zheng, X.; Lytle, R.A.; Higashikubo, R.; Rich, K.M. Lovastatin-induced up-regulation of the BH3-only protein, Bim, and cell death in glioblastoma cells. J. Neurochem., 2004, 89(1), 168-178. [].
Oliveira, K.A.; Dal-Cim, T.; Lopes, F.G.; Ludka, F.K.; Nedel, C.B.; Tasca, C.I. Atorvastatin promotes cytotoxicity and reduces migration and proliferation of human A172 glioma cells. Mol. Neurobiol., 2018, 55, 1509-1523.
Jiang, P.; Mukthavaram, R.; Chao, Y.; Bharati, I.S.; Fogal, V.; Pastorino, S.; Cong, X.; Nomura, N.; Gallagher, M.; Abbasi, T.; Vali, S.; Pingle, S.C.; Makale, M.; Kesari, S. Novel anti-glioblastoma agents and therapeutic combinations identified from a collection of FDA approved drugs. J. Transl. Med., 2014, 12, 13. [].
Kikuchi, T.; Nagata, Y.; Abe, T. In vitro and in vivo antiproliferative effects of simvastatin, an HMG-CoA reductase inhibitor, on human glioma cells. J. Neurooncol., 1997, 34(3), 233-239. [http://].
Larner, J.; Jane, J.; Laws, E.; Packer, R.; Myers, C.; Shaffrey, M. A phase I-II trial of lovastatin for anaplastic astrocytoma and glioblastoma multiforme. Am. J. Clin. Oncol., 1998, 21(6), 579-583. [].
Ferris, J.S.; McCoy, L.; Neugut, A.I.; Wrensch, M.; Lai, R. HMG CoA reductase inhibitors, NSAIDs and risk of glioma. Int. J. Cancer, 2012, 131(6), E1031-E1037. [].
Gaist, D.; Andersen, L.; Hallas, J.; Sorensen, H.T.; Schroder, H.D.; Friis, S. Use of statins and risk of glioma: a nationwide case-control study in Denmark. Br. J. Cancer, 2013, 108(3), 715-720. [].
Bhavsar, S.; Hagan, K.; Arunkumar, R.; Potylchansky, Y.; Grasu, R.; Dang, A.; Carlson, R.; Cowels, C.; Arnold, B.; Rahlfs, T.F.; Lipski, I.; Walsh, C.; Nguyen, A.T.; Feng, L.; Cata, J.P. Preoperative statin use is not associated with improvement in survival after glioblastoma surgery. J. Clin. Neurosci., 2016, 31, 176-180. [].
Butterick, T.A.; Igbavboa, U.; Eckert, G.P.; Sun, G.Y.; Weisman, G.A.; Muller, W.E.; Wood, W.G. Simvastatin stimulates production of the antiapoptotic protein Bcl-2 via endothelin-1 and NFATc3 in SH-SY5Y cells. Mol. Neurobiol., 2010, 41(2-3), 384-391. [].
Wang, H.X.; Gao, W.J. Cell type-specific development of NMDA receptors in the interneurons of rat prefrontal cortex. Neuropsychopharmacology, 2009, 34(8), 2028-2040. [ npp.2009.20].
Citraro, R.; Chimirri, S.; Aiello, R.; Gallelli, L.; Trimboli, F.; Britti, D.; De Sarro, G.; Russo, E. Protective effects of some statins on epileptogenesis and depressive-like behavior in WAG/Rij rats, a genetic animal model of absence epilepsy. Epilepsia, 2014, 55(8), 1284-1291. [].
Niehues da Cruz, J.l.; Delwing de Lima, D.; Delwing Dal Magro, D.b.; Geraldo Pereira da Cruz, J. The power of classic music to reduce anxiety in rats treated with simvastatin. Basic Clin. Neurosci., 2011, 2(4), 5-11.
Can, O.D.; Ulupinar, E.; Ozkay, U.D.; Yegin, B.; Ozturk, Y. The effect of simvastatin treatment on behavioral parameters, cognitive performance, and hippocampal morphology in rats fed a standard or a high-fat diet. Behav. Pharmacol., 2012, 23(5-6), 582-592. [].
Zanoli, P.; Rivasi, M.; Zavatti, M.; Brusiani, F.; Baraldi, M. New insight in the neuropharmacological activity of Humulus lupulus L. J. Ethnopharmacol., 2005, 102(1), 102-106. [ 1016/j.jep.2005.05.040].
Maggo, S.; Clark, D.; Ashton, J.C. The effect of statins on performance in the Morris water maze in guinea pig. Eur. J. Pharmacol., 2012, 674(2-3), 287-293. [ 2011.11.006].
File, S.E. Naloxone reduces social and exploratory activity in the rat. Psychopharmacology (Berl.), 1980, 71(1), 41-44. [http://dx.].
File, S.E.; Seth, P. A review of 25 years of the social interaction test. Eur. J. Pharmacol., 2003, 463(1-3), 35-53. [ 10.1016/S0014-2999(03)01273-1].
Pellow, S.; File, S.E. Anxiolytic and anxiogenic drug effects on exploratory activity in an elevated plus-maze: a novel test of anxiety in the rat. Pharmacol. Biochem. Behav., 1986, 24(3), 525-529. [].
Gonzalez, L.E.; Andrews, N.; File, S.E. 5-HT1A and benzodiazepine receptors in the basolateral amygdala modulate anxiety in the social interaction test, but not in the elevated plus-maze. Brain Res., 1996, 732(1-2), 145-153. [].
File, S. E. Usefulness of animal models with newer anxiolytics. Clin. Neuropharmacol., 1992. (15 Suppl )1 Pt A, 525A-526A,
Cheeta, S.; Kenny, P.J.; File, S.E. Hippocampal and septal injections of nicotine and 8-OH-DPAT distinguish among different animal tests of anxiety. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2000, 24(7), 1053-1067. [].
File, S.E.; Cheeta, S.; Kenny, P.J. Neurobiological mechanisms by which nicotine mediates different types of anxiety. Eur. J. Pharmacol., 2000, 393(1-3), 231-236. [].
File, S.E.; Lippa, A.S.; Beer, B.; Lippa, M.T. Animal tests of anxiety.Curr. Protoc. Neurosci; , 2004. Chapter 8, Unit 83,
File, S.E.; Hyde, J.R. Can social interaction be used to measure anxiety? Br. J. Pharmacol., 1978, 62(1), 19-24. [ 10.1111/j.1476-5381.1978.tb07001.x].
Heim, C.; Wagner, D.; Maloney, E.; Papanicolaou, D.A.; Solomon, L.; Jones, J.F.; Unger, E.R.; Reeves, W.C. Early adverse experience and risk for chronic fatigue syndrome: results from a population-based study. Arch. Gen. Psychiatry, 2006, 63(11), 1258-1266. [].
Kumar, A.; Vashist, A.; Kumar, P.; Kalonia, H.; Mishra, J. Protective effect of HMG CoA reductase inhibitors against running wheel activity induced fatigue, anxiety like behavior, oxidative stress and mitochondrial dysfunction in mice. Pharmacol. Rep., 2012, 64(6), 1326-1336. [].
Tonstad, S. Children and statins. Acta Paediatr., 2003, 92(9), 1001-1002. [].
Tuccori, M.; Lapi, F.; Testi, A.; Coli, D.; Moretti, U.; Vannacci, A.; Motola, D.; Salvo, F.; Rivolta, A.L.; Blandizzi, C.; Mugelli, A.; Del Tacca, M. Statin-associated psychiatric adverse events: a case/non-case evaluation of an Italian database of spontaneous adverse drug reaction reporting. Drug Saf., 2008, 31(12), 1115-1123. [].
Mansi, I.; Frei, C.R.; Pugh, M.J.; Mortensen, E.M. Psychologic disorders and statin use: a propensity score-matched analysis. Pharmacotherapy, 2013, 33(6), 615-626. [ 1002/phar.1272].
Hsia, J.; MacFadyen, J.G.; Monyak, J.; Ridker, P.M. Cardiovascular event reduction and adverse events among subjects attaining low-density lipoprotein cholesterol <50 mg/dl with rosuvastatin. The JUPITER trial (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin). J. Am. Coll. Cardiol., 2011, 57(16), 1666-1675. [ j.jacc.2010.09.082].
Pasco, J.A.; Nicholson, G.C.; Williams, L.J.; Jacka, F.N.; Henry, M.J.; Kotowicz, M.A.; Schneider, H.G.; Leonard, B.E.; Berk, M. Association of high-sensitivity C-reactive protein with de novo major depression. Br. J. Psychiatry, 2010, 197(5), 372-377. [http://].
Yang, C.C.; Jick, S.S.; Jick, H. Lipid-lowering drugs and the risk of depression and suicidal behavior. Arch. Intern. Med., 2003, 163(16), 1926-1932. [ 1926].
Chuang, C.S.; Yang, T.Y.; Muo, C.H.; Su, H.L.; Sung, F.C.
Kao, C.H. Hyperlipidemia, statin use and the risk of developing depression: a nationwide retrospective cohort study. Gen. Hosp. Psychiatry, 2014, 36(5), 497-501. [ j.genhosppsych.2014.05.008].
LeDoux, J.E. Emotion circuits in the brain. Annu. Rev. Neurosci., 2000, 23, 155-184. [].
Zaloshnja, E.; Miller, T.; Langlois, J.A.; Selassie, A.W. Prevalence of long-term disability from traumatic brain injury in the civilian population of the United States, 2005. J. Head Trauma Rehabil., 2008, 23(6), 394-400. [].
Allan, S.M.; Harrison, D.C.; Read, S.; Collins, B.; Parsons, A.A.; Philpott, K.; Rothwell, N.J. Selective increases in cytokine expression in the rat brain in response to striatal injection of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate and interleukin-1. Brain Res. Mol. Brain Res., 2001, 93(2), 180-189. [http://dx.doi. org/10.1016/S0169-328X(01)00211-X].
Zhang, Q.; Raoof, M.; Chen, Y.; Sumi, Y.; Sursal, T.; Junger, W.; Brohi, K.; Itagaki, K.; Hauser, C.J. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature, 2010, 464(7285), 104-107. [].
Miller, A.H.; Maletic, V.; Raison, C.L. Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol. Psychiatry, 2009, 65(9), 732-741. [http://dx.doi. org/10.1016/j.biopsych.2008.11.029].
Wajant, H.; Henkler, F.; Scheurich, P. The TNF-receptor-associated factor family: scaffold molecules for cytokine receptors, kinases and their regulators. Cell. Signal., 2001, 13(6), 389-400. [].
Kilic, F.S.; Ozatik, Y.; Kaygisiz, B.; Baydemir, C.; Erol, K. Acute antidepressant and anxiolytic effects of simvastatin and its mechanisms in rats. Neurosciences (Riyadh), 2012, 17(1), 39-43.
Lechleitner, M.; Hoppichler, F.; Konwalinka, G.; Patsch, J.R.; Braunsteiner, H. Depressive symptoms in hypercholesterolaemic patients treated with pravastatin. Lancet, 1992, 340(8824), 910. [].
Morales, K.; Wittink, M.; Datto, C.; DiFilippo, S.; Cary, M.; TenHave, T.; Katz, I.R. Simvastatin causes changes in affective processes in elderly volunteers. J. Am. Geriatr. Soc., 2006, 54(1), 70-76. [].
Hyyppa, M.T.; Kronholm, E.; Virtanen, A.; Leino, A.; Jula, A. Does simvastatin affect mood and steroid hormone levels in hypercholesterolemic men? A randomized double-blind trial. Psychoneuroendocrinology, 2003, 28(2), 181-194. [ S0306-4530(02)00014-8].
Osborn, D.P.; Nazareth, I.; King, M.B. Physical activity, dietary habits and Coronary Heart Disease risk factor knowledge amongst people with severe mental illness: a cross sectional comparative study in primary care. Soc. Psychiatry Psychiatr. Epidemiol., 2007, 42(10), 787-793. [].
Laursen, T.M.; Munk-Olsen, T.; Gasse, C. Chronic somatic comorbidity and excess mortality due to natural causes in persons with schizophrenia or bipolar affective disorder. PLoS One, 2011, 6(9), 1-7. [].
Berk, M.; Copolov, D.; Dean, O.; Lu, K.; Jeavons, S.; Schapkaitz, I.; Anderson-Hunt, M.; Judd, F.; Katz, F.; Katz, P.; Ording-Jespersen, S.; Little, J.; Conus, P.; Cuenod, M.; Do, K.Q.; Bush, A.I. N-acetyl cysteine as a glutathione precursor for schizophrenia--a double-blind, randomized, placebo-controlled trial. Biol. Psychiatry, 2008, 64(5), 361-368. [ 2008.03.004].
Chang, S.H.; Chiang, S.Y.; Chiu, C.C.; Tsai, C.C.; Tsai, H.H.; Huang, C.Y.; Hsu, T.C.; Tzang, B.S. Expression of anti-cardiolipin antibodies and inflammatory associated factors in patients with schizophrenia. Psychiatry Res., 2011, 187(3), 341-346. [http://dx.].
Song, X.Q.; Lv, L.X.; Li, W.Q.; Hao, Y.H.; Zhao, J.P. The interaction of nuclear factor-kappa B and cytokines is associated with schizophrenia. Biol. Psychiatry, 2009, 65(6), 481-488. [http://dx.].
Ghanizadeh, A.; Dehbozorgi, S.; Omrani, S.M.; Rezaei, Z. Minocycline as add-on treatment decreases the negative symptoms of schizophrenia; a randomized placebo-controlled clinical trial. Recent Pat. Inflamm. Allergy Drug Discov., 2014, 8(3), 211-215. [ 2174/1872213X08666141029123524].
Lilly, S.M.; Mortensen, E.M.; Frei, C.R.; Pugh, M.J.; Mansi, I.A. Comparison of the risk of psychological and cognitive disorders between persistent and nonpersistent statin users. Am. J. Cardiol., 2014, 114(7), 1035-1039. [ 07.010].
Zhao, J.; Zhang, X.; Dong, L.; Wen, Y.; Cui, L. The many roles of statins in ischemic stroke. Curr. Neuropharmacol., 2014, 12(6), 564-574. [].
Ni Chroinin, D.; Asplund, K.; Asberg, S.; Callaly, E.; Cuadrado-Godia, E.; Diez-Tejedor, E.; Di Napoli, M.; Engelter, S.T.; Furie, K.L.; Giannopoulos, S.; Gotto, A.M., Jr; Hannon, N.; Jonsson, F.; Kapral, M.K.; Marti-Fabregas, J.; Martinez-Sanchez, P.; Milionis, H.J.; Montaner, J.; Muscari, A.; Pikija, S.; Probstfield, J.; Rost, N.S.; Thrift, A.G.; Vemmos, K.; Kelly, P.J. Statin therapy and outcome after ischemic stroke: systematic review and meta-analysis of observational studies and randomized trials. Stroke, 2013, 44(2), 448-456. [].
Merwick, A.; Albers, G.W.; Arsava, E.M.; Ay, H.; Calvet, D.; Coutts, S.B.; Cucchiara, B.L.; Demchuk, A.M.; Giles, M.F.; Mas, J.L.; Olivot, J.M.; Purroy, F.; Rothwell, P.M.; Saver, J.L.; Sharma, V.K.; Tsivgoulis, G.; Kelly, P.J. Reduction in early stroke risk in carotid stenosis with transient ischemic attack associated with statin treatment. Stroke, 2013, 44(10), 2814-2820. [ 1161/STROKEAHA.113.001576].
Al-Khaled, M.; Matthis, C.; Eggers, J. Statin treatment in patients with acute ischemic stroke. Int. J. Stroke, 2014, 9(5), 597-601. [].
Flint, A.C.; Kamel, H.; Navi, B.B.; Rao, V.A.; Faigeles, B.S.; Conell, C.; Klingman, J.G.; Sidney, S.; Hills, N.K.; Sorel, M.
Cullen, S.P.; Johnston, S.C. Statin use during ischemic stroke hospitalization is strongly associated with improved poststroke survival. Stroke, 2012, 43(1), 147-154. [ STROKEAHA.111.627729].
Tonkin, A.; Simes, R.; Sharpe, N.; Thomson, A. The long term intervention with pravastatin in ischaemic disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N. Engl. J. Med., 1998, 339(19), 1349-1357. [].
Schwartz, G.G.; Olsson, A.G.; Ezekowitz, M.D.; Ganz, P.; Oliver, M.F.; Waters, D.; Zeiher, A.; Chaitman, B.R.; Leslie, S.; Stern, T. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. JAMA, 2001, 285(13), 1711-1718. [ jama.285.13.1711].
Sirol, M.; Bouzamondo, A.; Sanchez, P.; Lechat, P. Does statin therapy reduce the risk of stroke? A meta-analysis. Ann. Med. Interne (Paris), 2001, 152(3), 188-193.
Martinez-Sanchez, P.; Fuentes, B.; Martinez-Martinez, M.; Ruiz-Ares, G.; Fernandez-Travieso, J.; Sanz-Cuesta, B.E.; Cuellar-Gamboa, L.; Diaz-Dominguez, E.; Diez-Tejedor, E. Treatment with statins and ischemic stroke severity: does the dose matter? Neurology, 2013, 80(19), 1800-1805. [ 0b013e3182918d38].
Endres, M.; Laufs, U.; Huang, Z.; Nakamura, T.; Huang, P.; Moskowitz, M.A.; Liao, J.K. Stroke protection by 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors mediated by endothelial nitric oxide synthase. Proc. Natl. Acad. Sci. USA, 1998, 95(15), 8880-8885. [].
Kureishi, Y.; Luo, Z.; Shiojima, I.; Bialik, A.; Fulton, D.; Lefer, D.J.; Sessa, W.C.; Walsh, K. The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals. Nat. Med., 2000, 6(9), 1004-1010. [].
Laufs, U.; Liao, J.K. Post-transcriptional regulation of endothelial nitric oxide synthase mRNA stability by Rho GTPase. J. Biol. Chem., 1998, 273(37), 24266-24271. [ jbc.273.37.24266].
Shao, S.; Xu, M.; Zhou, J.; Ge, X.; Chen, G.; Guo, L.; Luo, L.; Li, K.; Zhu, Z.; Zhang, F. Atorvastatin attenuates ischemia/ reperfusion-induced hippocampal neurons injury Via Akt-nNOS-JNK signaling pathway. Cell. Mol. Neurobiol., 2017, 37(4), 753-762. [].
Gasche, Y.; Copin, J.C.; Sugawara, T.; Fujimura, M.; Chan, P.H. Matrix metalloproteinase inhibition prevents oxidative stress-associated blood-brain barrier disruption after transient focal cerebral ischemia. J. Cereb. Blood Flow Metab., 2001, 21(12), 1393-1400. [].
Woo, M.S.; Park, J.S.; Choi, I.Y.; Kim, W.K.; Kim, H.S. Inhibition of MMP-3 or -9 suppresses lipopolysaccharide-induced expression of proinflammatory cytokines and iNOS in microglia. J. Neurochem., 2008, 106(2), 770-780. [].
Liu, X.S.; Zhang, Z.G.; Zhang, L.; Morris, D.C.; Kapke, A.; Lu, M.; Chopp, M. Atorvastatin downregulates tissue plasminogen activator-aggravated genes mediating coagulation and vascular permeability in single cerebral endothelial cells captured by laser microdissection. J. Cereb. Blood Flow Metab., 2006, 26(6), 787-796. [].
Wang, S.; Lee, S.R.; Guo, S.Z.; Kim, W.J.; Montaner, J.
Wang, X.; Lo, E.H. Reduction of tissue plasminogen activator-induced matrix metalloproteinase-9 by simvastatin in astrocytes. Stroke, 2006, 37(7), 1910-1912. [ 0000226923.48905.39].
Sironi, L.; Banfi, C.; Brioschi, M.; Gelosa, P.; Guerrini, U.; Nobili, E.; Gianella, A.; Paoletti, R.; Tremoli, E.; Cimino, M. Activation of NF-kB and ERK1/2 after permanent focal ischemia is abolished by simvastatin treatment. Neurobiol. Dis., 2006, 22(2), 445-451. [].
Hong, H.; Zeng, J.S.; Kreulen, D.L.; Kaufman, D.I.; Chen, A.F. Atorvastatin protects against cerebral infarction via inhibition of NADPH oxidase-derived superoxide in ischemic stroke. Am. J. Physiol. Heart Circ. Physiol., 2006, 291(5), H2210-H2215. [].
De Caterina, R.; Salvatore, T.; Marchioli, R. Cholesterol-lowering interventions and stroke: Insights from IMPROVE-IT. Atherosclerosis, 2016, 248, 216-218. [ 2016.03.024].

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