Generic placeholder image

Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Reviewing Biochemical Implications of Normal and Mutated Huntingtin in Huntington’s Disease

Author(s): Ester Tellone*, Antonio Galtieri and Silvana Ficarra

Volume 27, Issue 31, 2020

Page: [5137 - 5158] Pages: 22

DOI: 10.2174/0929867326666190621101909

Price: $65


Huntingtin (Htt) is a multi-function protein of the brain. Normal Htt shows a common alpha-helical structure but conformational changes in the form with beta strands are the principal cause of Huntington’s disease. Huntington’s disease is a genetic neurological disorder caused by a repeated expansion of the CAG trinucleotide, causing instability in the N-terminal of the gene coding for the Huntingtin protein. The mutation leads to the abnormal expansion of the production of the polyglutamine tract (polyQ) resulting in the form of an unstable Huntingtin protein commonly referred to as mutant Huntingtin. Mutant Huntingtin is the cause of the complex neurological metabolic alteration of Huntington’s disease, resulting in both the loss of all the functions of normal Huntingtin and the genesis of abnormal interactions due to the presence of this mutation. One of the problems arising from the misfolded Huntingtin is the increase in oxidative stress, which is common in many neurological diseases such as Alzheimer’s, Parkinson’s, Amyotrophic Lateral Sclerosis and Creutzfeldt-Jakob disease. In the last few years, the use of antioxidants had a strong incentive to find valid therapies for defence against neurodegenerations. Although further studies are needed, the use of antioxidant mixtures to counteract neuronal damages seems promising.

Keywords: Huntington's disease, Huntingtin, neurodegeneration, misfolding, antioxidants, oxidative stress.

Reeve, A.; Simcox, E.; Turnbull, D. Ageing and Parkinson’s disease: why is advancing age the biggest risk factor? Ageing Res. Rev., 2014, 14(100), 19-30.
[] [PMID: 24503004]
Wyss-Coray, T. Ageing, neurodegeneration and brain rejuvenation. Nature, 2016, 539(7628), 180-186.
[] [PMID: 27830812]
Hung, C.W.; Chen, Y.C.; Hsieh, W.L.; Chiou, S.H.; Kao, C.L. Ageing and neurodegenerative diseases. Ageing Res. Rev., 2010, 9(1)(Suppl. 1), S36-S46.
[] [PMID: 20732460]
Kawas, C.H.; Kim, R.C.; Sonnen, J.A.; Bullain, S.S.; Trieu, T.; Corrada, M.M. Multiple pathologies are common and related to dementia in the oldest-old: the 90+ study. Neurology, 2015, 85(6), 535-542.
[] [PMID: 26180144]
Liguori, I.; Russo, G.; Curcio, F.; Bulli, G.; Aran, L.; Della-Morte, D.; Gargiulo, G.; Testa, G.; Cacciatore, F.; Bonaduce, D.; Abete, P. Oxidative stress, aging, and diseases. Clin. Interv. Aging, 2018, 13, 757-772.
[] [PMID: 29731617]
Niedzielska, E.; Smaga, I.; Gawlik, M.; Moniczewski, A.; Stankowicz, P.; Pera, J.; Filip, M. Oxidative stress in neurodegenerative diseases. Mol. Neurobiol., 2016, 53(6), 4094-4125.
[] [PMID: 26198567]
Liu, Z.; Zhou, T.; Ziegler, A.C.; Dimitrion, P.; Zuo, L. Oxidative stress in neurodegenerative diseases: from molecular mechanisms to clinical applications. Oxid. Med. Cell. Longevity, 2017, 2017, 2.
[] [PMID: 28785371]
Andersen, J.K. Oxidative stress in neurodegeneration: cause or consequence? Nat. Med., 2004, 10(Suppl.), S18-S25.
[] [PMID: 15298006]
Lalkovičová, M.; Danielisová, V. Neuroprotection and antioxidants. Neural Regen. Res., 2016, 11(6), 865-874.
[] [PMID: 27482198]
Cobley, J.N.; Fiorello, M.L.; Bailey, D.M. 13 reasons why the brain is susceptible to oxidative stress. Redox Biol., 2018, 15, 490-503.
[] [PMID: 29413961]
Popescu, B.F.G.; Nichol, H. Mapping brain metals to evaluate therapies for neurodegenerative disease. CNS Neurosci. Ther., 2011, 17(4), 256-268.
[] [PMID: 20553312]
Bentsen, H. Dietary polyunsaturated fatty acids, brain function and mental health. Microb. Ecol. Health Dis., 2017, 28(1) 1281916
[ ]
Lobo, V.; Patil, A.; Phatak, A.; Chandra, N. Free radicals, antioxidants and functional foods: impact on human health. Pharmacogn. Rev., 2010, 4(8), 118-126.
[] [PMID: 22228951]
Carvalho, J.C.T.; Fernandes, C.P.; Daleprane, J.B.; Alves, M.S.; Stien, D.; Dhammika Nanayakkara, N.P. Role of natural antioxidants from functional foods in neurodegenerative and metabolic disorders. Oxid. Med. Cell. Longev., 2018, 2018 1459753
[] [PMID: 30405873]
Chang, B.J.; Jang, B.J.; Son, T.G.; Cho, I.H.; Quan, F.S.; Choe, N.H.; Nahm, S.S.; Lee, J.H. Ascorbic acid ameliorates oxidative damage induced by maternal low-level lead exposure in the hippocampus of rat pups during gestation and lactation. Food Chem. Toxicol., 2012, 50(2), 104-8.
[] [PMID: 22056337]
Roos, R.A.C. Huntington’s disease: a clinical review. Orphanet J. Rare Dis., 2010, 5, 40.
[] [PMID: 21171977]
Langbehn, D.R.; Hayden, M.R.; Paulsen, J.S. and the PREDICT-HD Investigators of the Huntington Study Group. CAG-repeat length and the age of onset in Huntington disease (HD): a review and validation study of statistical approaches. Am. J. Med. Genet. B. Neuropsychiatr. Genet., 2010, 153B(2), 397-408.
[] [PMID: 19548255]
Eidelberg, D.; Surmeier, D.J. Brain networks in Huntington disease. J. Clin. Invest., 2011, 121(2), 484-492.
[] [PMID: 21285521]
Ross, C.A.; Tabrizi, S.J. Huntington’s disease: from molecular pathogenesis to clinical treatment. Lancet Neurol., 2011, 10(1), 83-98.
[] [PMID: 21163446]
Pringsheim, T.; Wiltshire, K.; Day, L.; Dykeman, J.; Steeves, T.; Jette, N. The incidence and prevalence of Huntington’s disease: a systematic review and meta-analysis. Mov. Disord., 2012, 27(9), 1083-1091.
[] [PMID: 22692795]
Dorsey, E.R.; Beck, C.A.; Darwin, K.; Nichols, P.; Brocht, A.F.; Biglan, K.M.; Shoulson, I. Huntington Study Group COHORT Investigators. Natural history of Huntington disease. JAMA Neurol., 2013, 70(12), 1520-1530.
[] [PMID: 24126537]
Labbadia, J.; Morimoto, R.I. Huntington’s disease: underlying molecular mechanisms and emerging concepts. Trends Biochem. Sci., 2013, 38(8), 378-385.
[] [PMID: 23768628]
Ross, C.A.; Aylward, E.H.; Wild, E.J.; Langbehn, D.R.; Long, J.D.; Warner, J.H.; Scahill, R.I.; Leavitt, B.R.; Stout, J.C.; Paulsen, J.S.; Reilmann, R.; Unschuld, P.G.; Wexler, A.; Margolis, R.L.; Tabrizi, S.J. Huntington disease: natural history, biomarkers and prospects for therapeutics. Nat. Rev. Neurol., 2014, 10(4), 204-216.
[] [PMID: 24614516]
Bates, G.P.; Dorsey, R.; Gusella, J.F.; Hayden, M.R.; Kay, C.; Leavitt, B.R.; Nance, M.; Ross, C.A.; Scahill, R.I.; Wetzel, R.; Wild, E.J.; Tabrizi, S.J. Huntington disease. Nat. Rev. Dis. Primers, 2015, 1(23), 15005.
[] [PMID: 27188817]
Huang, W.J.; Chen, W.W.; Zhang, X. Huntington’s disease: molecular basis of pathology and status of current therapeutic approaches. Exp. Ther. Med., 2016, 12(4), 1951-1956.
[] [PMID: 27698679]
Sun, Y.M.; Zhang, Y.B.; Wu, Z.Y. Huntington’s disease: relationship between phenotype and genotype. Mol. Neurobiol., 2017, 54(1), 342-348.
[] [PMID: 26742514]
McColgan, P.; Tabrizi, S.J. Huntington’s disease: a clinical review. Eur. J. Neurol., 2018, 25(1), 24-34.
[] [PMID: 28817209]
Zheng, J.; Winderickx, J.; Franssens, V.; Liu, B. A mitochondria-associated oxidative stress perspective on Huntington’s disease. Front. Mol. Neurosci., 2018, 11, 329.
[] [PMID: 30283298]
Hofer, S.; Kainz, K.; Zimmermann, A.; Bauer, M.A.; Pendl, T.; Poglitsch, M.; Madeo, F.; Carmona-Gutierrez, D. Studying Huntington’s disease in yeast: from mechanisms to pharmacological approaches. Front. Mol. Neurosci., 2018, 11(11), 318.
[] [PMID: 30233317]
Myers, R.H.; MacDonald, M.E.; Koroshetz, W.J.; Duyao, M.P.; Ambrose, C.M.; Taylor, S.A.; Barnes, G.; Srinidhi, J.; Lin, C.S.; Whaley, W.L. De novo expansion of a (CAG)n repeat in sporadic Huntington’s disease. Nat. Genet., 1993, 5(2), 168-173.
[] [PMID: 8252042]
Bates, G. Huntingtin aggregation and toxicity in Huntington’s disease. Lancet, 2003, 361(9369), 1642-1644.
[] [PMID: 12747895]
The Huntington’s Disease Collaborative Research Group. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. Cell, 1993, 72(6), 971-983.
[] [PMID: 8458085]
Andrew, S.E.; Goldberg, Y.P.; Theilmann, J.; Zeisler, J.; Hayden, M.R. A CCG repeat polymorphism adjacent to the CAG repeat in the Huntington disease gene: implications for diagnostic accuracy and predictive testing. Hum. Mol. Genet., 1994, 3(1), 65-67.
[] [PMID: 8162053]
Cannella, M.; Gellera, C.; Maglione, V.; Giallonardo, P.; Cislaghi, G.; Muglia, M.; Quattrone, A.; Pierelli, F.; Di Donato, S.; Squitieri, F. The gender effect in juvenile Huntington disease patients of Italian origin. Am. J. Med. Genet. B. Neuropsychiatr. Genet., 2004, 125B(1), 92-98.
[] [PMID: 14755452]
Ranen, N.G.; Stine, O.C.; Abbott, M.H.; Sherr, M.; Codori, A.M.; Franz, M.L.; Chao, N.I.; Chung, A.S.; Pleasant, N.; Callahan, C. Anticipation and instability of IT-15 (CAG)n repeats in parent-offspring pairs with Huntington disease. Am. J. Hum. Genet., 1995, 57(3), 593-602.
[PMID: 7668287]
Pearson, C.E. Slipping while sleeping? Trinucleotide repeat expansions in germ cells. Trends Mol. Med., 2003, 9(11), 490-495.
[] [PMID: 14604827]
Perutz, M.F.; Johnson, T.; Suzuki, M.; Finch, J.T. Glutamine repeats as polar zippers: their possible role in inherited neurodegenerative diseases. Proc. Natl. Acad. Sci. USA, 1994, 91(12), 5355-5358.
[] [PMID: 8202492]
Li, S.H.; Li, X.J. Huntingtin-protein interactions and the pathogenesis of Huntington’s disease. Trends Genet., 2004, 20(3), 146-154.
[] [PMID: 15036808]
Kim, M.W.; Chelliah, Y.; Kim, S.W.; Otwinowski, Z.; Bezprozvanny, I. Secondary structure of huntingtin amino-terminal region. Structure, 2009, 17(9), 1205-1212.
[] [PMID: 19748341]
Zuccato, C.; Valenza, M.; Cattaneo, E. Molecular mechanisms and potential therapeutical targets in Huntington’s disease. Physiol. Rev., 2010, 90(3), 905-981.
[] [PMID: 20664076]
Zoghbi, H.Y.; Orr, H.T. Glutamine repeats and neurodegeneration. Annu. Rev. Neurosci., 2000, 23, 217-247.
[] [PMID: 10845064]
Martí, E. RNA toxicity induced by expanded CAG repeats in Huntington’s disease. Brain Pathol., 2016, 26(6), 779-786.
[] [PMID: 27529325]
Steffan, J.S.; Kazantsev, A.; Spasic-Boskovic, O.; Greenwald, M.; Zhu, Y.Z.; Gohler, H.; Wanker, E.E.; Bates, G.P.; Housman, D.E.; Thompson, L.M. The Huntington’s disease protein interacts with p53 and CREB-binding protein and represses transcription. Proc. Natl. Acad. Sci. USA, 2000, 97(12), 6763-6768.
[] [PMID: 10823891]
Nucifora, F.C., Jr; Sasaki, M.; Peters, M.F.; Huang, H.; Cooper, J.K.; Yamada, M.; Takahashi, H.; Tsuji, S.; Troncoso, J.; Dawson, V.L.; Dawson, T.M.; Ross, C.A. Interference by huntingtin and atrophin-1 with cbp-mediated transcription leading to cellular toxicity. Science, 2001, 291(5512), 2423-2428.
[] [PMID: 11264541]
Lee, W.; Reyes, R.C.; Gottipati, M.K.; Lewis, K.; Lesort, M.; Parpura, V.; Gray, M. Enhanced Ca(2+)-dependent glutamate release from astrocytes of the BACHD Huntington’s disease mouse model. Neurobiol. Dis., 2013, 58, 192-199.
[] [PMID: 23756199]
Arndt, J.R.; Chaibva, M.; Legleiter, J. The emerging role of the first 17 amino acids of huntingtin in Huntington’s disease. Biomol. Concepts, 2015, 6(1), 33-46.
[] [PMID: 25741791]
Rockabrand, E.; Slepko, N.; Pantalone, A.; Nukala, V.N.; Kazantsev, A.; Marsh, J.L.; Sullivan, P.G.; Steffan, J.S.; Sensi, S.L.; Thompson, L.M. The first 17 amino acids of huntingtin modulate its sub-cellular localization, aggregation and effects on calcium homeostasis. Hum. Mol. Genet., 2007, 16(1), 61-77.
[] [PMID: 17135277]
Atwal, R.S.; Truant, R. A stress sensitive ER membrane-association domain in huntingtin protein defines a potential role for huntingtin in the regulation of autophagy. Autophagy, 2008, 4(1), 91-93.
[] [PMID: 17986868]
Maiuri, T.; Woloshansky, T.; Xia, J.; Truant, R. The huntingtin N17 domain is a multifunctional CRM1 and Ran-dependent nuclear and cilial export signal. Hum. Mol. Genet., 2013, 22(7), 1383-1394.
[] [PMID: 23297360]
Zheng, Z.; Li, A.; Holmes, B.B.; Marasa, J.C.; Diamond, M.I. An N-terminal nuclear export signal regulates trafficking and aggregation of huntingtin (Htt) protein exon 1. J. Biol. Chem., 2013, 288(9), 6063-6071.
[] [PMID: 23319588]
Xia, J.; Lee, D.H.; Taylor, J.; Vandelft, M.; Truant, R. Huntingtin contains a highly conserved nuclear export signal. Hum. Mol. Genet., 2003, 12(12), 1393-1403.
[] [PMID: 12783847]
Atwal, R.S.; Desmond, C.R.; Caron, N.; Maiuri, T.; Xia, J.; Sipione, S.; Truant, R. Kinase inhibitors modulate huntingtin cell localization and toxicity. Nat. Chem. Biol., 2011, 7(7), 453-460.
[] [PMID: 21623356]
Havel, L.S.; Wang, C.E.; Wade, B.; Huang, B.; Li, S.; Li, X.J. Preferential accumulation of N-terminal mutant huntingtin in the nuclei of striatal neurons is regulated by phosphorylation. Hum. Mol. Genet., 2011, 20(7), 1424-1437.
[] [PMID: 21245084]
Ignatova, Z.; Gierasch, L.M. Inhibition of protein aggregation in vitro and in vivo by a natural osmoprotectant. Proc. Natl. Acad. Sci. USA, 2006, 103(36), 13357-13361.
[] [PMID: 16899544]
Bhattacharyya, A.; Thakur, A.K.; Chellgren, V.M.; Thiagarajan, G.; Williams, A.D.; Chellgren, B.W.; Creamer, T.P.; Wetzel, R. Oligoproline effects on polyglutamine conformation and aggregation. J. Mol. Biol., 2006, 355(3), 524-535.
[] [PMID: 16321399]
Andrade, M.A.; Bork, P. HEAT repeats in the Huntington’s disease protein. Nat. Genet., 1995, 11(2), 115-116.
[] [PMID: 7550332]
Takano, H.; Gusella, J.F. The predominantly HEAT-like motif structure of huntingtin and its association and coincident nuclear entry with dorsal, an NF-kB/Rel/dorsal family transcription factor. BMC Neurosci., 2002, 3(1), 15.
[] [PMID: 12379151]
Jones, L. Huntingtin-interacting proteins and their relevance to Huntington’s disease etiology. Neurosci. News, 2000, 3, 55-63.
Palidwor, G.A.; Shcherbinin, S.; Huska, M.R.; Rasko, T.; Stelzl, U.; Arumughan, A.; Foulle, R.; Porras, P.; Sanchez-Pulido, L.; Wanker, E.E.; Andrade-Navarro, M.A. Detection of alpha-rod protein repeats using a neural network and application to huntingtin. PLOS Comput. Biol., 2009, 5(3) e1000304
[] [PMID: 19282972]
Graham, R.K.; Deng, Y.; Slow, E.J.; Haigh, B.; Bissada, N.; Lu, G.; Pearson, J.; Shehadeh, J.; Bertram, L.; Murphy, Z.; Warby, S.C.; Doty, C.N.; Roy, S.; Wellington, C.L.; Leavitt, B.R.; Raymond, L.A.; Nicholson, D.W.; Hayden, M.R. Cleavage at the caspase-6 site is required for neuronal dysfunction and degeneration due to mutant huntingtin. Cell, 2006, 125(6), 1179-1191.
[] [PMID: 16777606]
Kim, Y.J.; Yi, Y.; Sapp, E.; Wang, Y.; Cuiffo, B.; Kegel, K.B.; Qin, Z.H.; Aronin, N.; DiFiglia, M. Caspase 3-cleaved N-terminal fragments of wild-type and mutant huntingtin are present in normal and Huntington’s disease brains, associate with membranes, and undergo calpain-dependent proteolysis. Proc. Natl. Acad. Sci. USA, 2001, 98(22), 12784-12789.
[] [PMID: 11675509]
Wellington, C.L.; Ellerby, L.M.; Gutekunst, C.A.; Rogers, D.; Warby, S.; Graham, R.K.; Loubser, O.; van Raamsdonk, J.; Singaraja, R.; Yang, Y.Z.; Gafni, J.; Bredesen, D.; Hersch, S.M.; Leavitt, B.R.; Roy, S.; Nicholson, D.W.; Hayden, M.R. Caspase cleavage of mutant huntingtin precedes neurodegeneration in Huntington’s disease. J. Neurosci., 2002, 22(18), 7862-7872.
[] [PMID: 12223539]
Lunkes, A.; Lindenberg, K.S.; Ben-Haïem, L.; Weber, C.; Devys, D.; Landwehrmeyer, G.B.; Mandel, J.L.; Trottier, Y. Proteases acting on mutant huntingtin generate cleaved products that differentially build up cytoplasmic and nuclear inclusions. Mol. Cell, 2002, 10(2), 259-269.
[] [PMID: 12191472]
Graham, R.K.; Deng, Y.; Carroll, J.; Vaid, K.; Cowan, C.; Pouladi, M.A.; Metzler, M.; Bissada, N.; Wang, L.; Faull, R.L.M.; Gray, M.; Yang, X.W.; Raymond, L.A.; Hayden, M.R. Cleavage at the 586 amino acid caspase-6 site in mutant huntingtin influences caspase-6 activation in vivo. J. Neurosci., 2010, 30(45), 15019-15029.
[] [PMID: 21068307]
Warby, S.C.; Doty, C.N.; Graham, R.K.; Carroll, J.B.; Yang, Y.Z.; Singaraja, R.R.; Overall, C.M.; Hayden, M.R. Activated caspase-6 and caspase-6-cleaved fragments of huntingtin specifically colocalize in the nucleus. Hum. Mol. Genet., 2008, 17(15), 2390-2404.
[] [PMID: 18445618]
Waldron-Roby, E.; Ratovitski, T.; Wang, X.; Jiang, M.; Watkin, E.; Arbez, N.; Graham, R.K.; Hayden, M.R.; Hou, Z.; Mori, S.; Swing, D.; Pletnikov, M.; Duan, W.; Tessarollo, L.; Ross, C.A. Transgenic mouse model expressing the caspase 6 fragment of mutant huntingtin. J. Neurosci., 2012, 32(1), 183-193.
[] [PMID: 22219281]
El-Daher, M.T.; Hangen, E.; Bruyère, J.; Poizat, G.; Al-Ramahi, I.; Pardo, R.; Bourg, N.; Souquere, S.; Mayet, C.; Pierron, G.; Lévêque-Fort, S.; Botas, J.; Humbert, S.; Saudou, F. Huntingtin proteolysis releases non-polyQ fragments that cause toxicity through dynamin 1 dysregulation. EMBO J., 2015, 34(17), 2255-2271.
[] [PMID: 26165689]
Jimenez-Sanchez, M.; Rubinsztein, D.C. Huntington’s disease-the sting in the tail. EMBO J., 2015, 34(17), 2215-2216.
[] [PMID: 26224597]
Luo, S.; Vacher, C.; Davies, J.E.; Rubinsztein, D.C. Cdk5 phosphorylation of huntingtin reduces its cleavage by caspases: implications for mutant huntingtin toxicity. J. Cell Biol., 2005, 169(4), 647-656.
[] [PMID: 15911879]
Schilling, B.; Gafni, J.; Torcassi, C.; Cong, X.; Row, R.H.; LaFevre-Bernt, M.A.; Cusack, M.P.; Ratovitski, T.; Hirschhorn, R.; Ross, C.A.; Gibson, B.W.; Ellerby, L.M. Huntingtin phosphorylation sites mapped by mass spectrometry. Modulation of cleavage and toxicity. J. Biol. Chem., 2006, 281(33), 23686-23697.
[] [PMID: 16782707]
Thompson, L.M.; Aiken, C.T.; Kaltenbach, L.S.; Agrawal, N.; Illes, K.; Khoshnan, A.; Martinez-Vincente, M.; Arrasate, M.; O’Rourke, J.G.; Khashwji, H.; Lukacsovich, T.; Zhu, Y.Z.; Lau, A.L.; Massey, A.; Hayden, M.R.; Zeitlin, S.O.; Finkbeiner, S.; Green, K.N.; LaFerla, F.M.; Bates, G.; Huang, L.; Patterson, P.H.; Lo, D.C.; Cuervo, A.M.; Marsh, J.L.; Steffan, J.S. IKK phosphorylates huntingtin and targets it for degradation by the proteasome and lysosome. J. Cell Biol., 2009, 187(7), 1083-1099.
[] [PMID: 20026656]
Khoshnan, A.; Patterson, P.H. The role of IκB kinase complex in the neurobiology of Huntington’s disease. Neurobiol. Dis., 2011, 43(2), 305-311.
[] [PMID: 21554955]
Watkin, E.E.; Arbez, N.; Waldron-Roby, E.; O’Meally, R.; Ratovitski, T.; Cole, R.N.; Ross, C.A. Phosphorylation of mutant huntingtin at serine 116 modulates neuronal toxicity. PLoS One, 2014, 9(2) e88284
[] [PMID: 24505464]
Mishra, R.; Hoop, C.L.; Kodali, R.; Sahoo, B.; van der Wel, P.C.; Wetzel, R. Serine phosphorylation suppresses huntingtin amyloid accumulation by altering protein aggregation properties. J. Mol. Biol., 2012, 424(1-2), 1-14.
[] [PMID: 22999956]
Jablonski, M.R.; Cooper, L.; Jacob, D.A. NMDA receptor excitotoxicity: impact on phosphatase activity and phosphorylation of huntingtin. J. Neurosci., 2011, 31(12), 4357-4359.
[] [PMID: 21430136]
Wilkinson, K.A.; Nakamura, Y.; Henley, J.M. Targets and consequences of protein SUMOylation in neurons. Brain Res. Brain Res. Rev., 2010, 64(1), 195-212.
[] [PMID: 20382182]
Gareau, J.R.; Lima, C.D. The SUMO pathway: emerging mechanisms that shape specificity, conjugation and recognition. Nat. Rev. Mol. Cell Biol., 2010, 11(12), 861-871.
[] [PMID: 21102611]
Johnson, E.S. Protein modification by SUMO. Annu. Rev. Biochem., 2004, 73, 355-382.
[] [PMID: 15189146]
Bohren, K.M.; Nadkarni, V.; Song, J.H.; Gabbay, K.H.; Owerbach, D.A. M55V polymorphism in a novel SUMO gene (SUMO-4) differentially activates heat shock transcription factors and is associated with susceptibility to type I diabetes mellitus. J. Biol. Chem., 2004, 279(26), 27233-27238.
[] [PMID: 15123604]
O’Rourke, J.G.; Gareau, J.R.; Ochaba, J.; Song, W.; Raskó, T.; Reverter, D.; Lee, J.; Monteys, A.M.; Pallos, J.; Mee, L.; Vashishtha, M.; Apostol, B.L.; Nicholson, T.P.; Illes, K.; Zhu, Y.Z.; Dasso, M.; Bates, G.P.; Difiglia, M.; Davidson, B.; Wanker, E.E.; Marsh, J.L.; Lima, C.D.; Steffan, J.S.; Thompson, L.M. SUMO-2 and PIAS1 modulate insoluble mutant huntingtin protein accumulation. Cell Rep., 2013, 4(2), 362-375.
[] [PMID: 23871671]
Kim, Y.M.; Jang, W.H.; Quezado, M.M.; Oh, Y.; Chung, K.C.; Junn, E.; Mouradian, M.M. Proteasome inhibition induces α-synuclein SUMOylation and aggregate formation. J. Neurol. Sci., 2011, 307(1-2), 157-161.
[] [PMID: 21641618]
Tatham, M.H.; Matic, I.; Mann, M.; Hay, R.T. Comparative proteomic analysis identifies a role for SUMO in protein quality control. Sci. Signal., 2011, 4(178), rs4.
[] [PMID: 21693764]
Subramaniam, S.; Mealer, R.G.; Sixt, K.M.; Barrow, R.K.; Usiello, A.; Snyder, S.H. Rhes, a physiologic regulator of sumoylation, enhances cross-sumoylation between the basic sumoylation enzymes E1 and Ubc9. J. Biol. Chem., 2010, 285(27), 20428-20432.
[] [PMID: 20424159]
Falk, J.D.; Vargiu, P.; Foye, P.E.; Usui, H.; Perez, J.; Danielson, P.E.; Lerner, D.L.; Bernal, J.; Sutcliffe, J.G. Rhes: A striatal-specific Ras homolog related to Dexras1. J. Neurosci. Res., 1999, 57(6), 782-788.
[<782:AID-JNR3>3.0.CO;2-9] [PMID: 10467249]
Pellegrino, S.; Altmeyer, M. Interplay between ubiquitin, SUMO and Poly(ADP-Ribose) in the cellular response to genotoxic stress. Front. Genet., 2016, 7, 63.
[] [PMID: 27148359]
Lin, X.; Liang, M.; Liang, Y.Y.; Brunicardi, F.C.; Feng, X.H. SUMO-1/Ubc9 promotes nuclear accumulation and metabolic stability of tumor suppressor Smad4. J. Biol. Chem., 2003, 278(33), 31043-31048.
[] [PMID: 12813045]
Feligioni, M.; Marcelli, S.; Knock, E.; Nadeem, U.; Arancio, O.; Fraser, P.E. SUMO modulation of protein aggregation and degradation. AIMS Mol. Sci., 2015, 2(4), 382-410.
Ehrnhoefer, D.E.; Sutton, L.; Hayden, M.R. Small changes, big impact: posttranslational modifications and function of huntingtin in Huntington disease. Neuroscientist, 2011, 17(5), 475-492.
[] [PMID: 21311053]
Huang, K.; Sanders, S.; Singaraja, R.; Orban, P.; Cijsouw, T.; Arstikaitis, P.; Yanai, A.; Hayden, M.R.; El-Husseini, A. Neuronal palmitoyl acyl transferases exhibit distinct substrate specificity. FASEB J., 2009, 23(8), 2605-2615.
[] [PMID: 19299482]
Yanai, A.; Huang, K.; Kang, R.; Singaraja, R.R.; Arstikaitis, P.; Gan, L.; Orban, P.C.; Mullard, A.; Cowan, C.M.; Raymond, L.A.; Drisdel, R.C.; Green, W.N.; Ravikumar, B.; Rubinsztein, D.C.; El-Husseini, A.; Hayden, M.R. Palmitoylation of huntingtin by HIP14 is essential for its trafficking and function. Nat. Neurosci., 2006, 9(6), 824-831.
[] [PMID: 16699508]
Fukata, Y.; Fukata, M. Protein palmitoylation in neuronal development and synaptic plasticity. Nat. Rev. Neurosci., 2010, 11(3), 161-175.
[] [PMID: 20168314]
Jeong, H.; Then, F.; Melia, T.J., Jr; Mazzulli, J.R.; Cui, L.; Savas, J.N.; Voisine, C.; Paganetti, P.; Tanese, N.; Hart, A.C.; Yamamoto, A.; Krainc, D. Acetylation targets mutant huntingtin to autophagosomes for degradation. Cell, 2009, 137(1), 60-72.
[] [PMID: 19345187]
Harjes, P.; Wanker, E.E. The hunt for huntingtin function: interaction partners tell many different stories. Trends Biochem. Sci., 2003, 28(8), 425-433.
[] [PMID: 12932731]
Zurawel, A.A.; Kabeche, R.; Di Gregorio, S.E.; Deng, L.; Menon, K.M.; Opalko, H.; Duennwald, M.L.; Moseley, J.B.; Supattapone, S. CAG expansions are genetically stable and form nontoxic aggregates in cells lacking endogenous polyglutamine proteins. MBio, 2016, 7(5), e01367-e013616.
[] [PMID: 27677791]
Cattaneo, E.; Rigamonti, D.; Goffredo, D.; Zuccato, C.; Squitieri, F.; Sipione, S. Loss of normal huntingtin function: new developments in Huntington’s disease research. Trends Neurosci., 2001, 24(3), 182-188.
[] [PMID: 11182459]
Cosker, K.E.; Courchesne, S.L.; Segal, R.A. Action in the axon: generation and transport of signaling endosomes. Curr. Opin. Neurobiol., 2008, 18(3), 270-275.
[] [PMID: 18778772]
Ha, J.; Lo, K.W.; Myers, K.R.; Carr, T.M.; Humsi, M.K.; Rasoul, B.A.; Segal, R.A.; Pfister, K.K. A neuron-specific cytoplasmic dynein isoform preferentially transports TrkB signaling endosomes. J. Cell Biol., 2008, 181(6), 1027-1039.
[] [PMID: 18559670]
Baydyuk, M.; Russell, T.; Liao, G.Y.; Zang, K.; An, J.J.; Reichardt, L.F.; Xu, B. TrkB receptor controls striatal formation by regulating the number of newborn striatal neurons. Proc. Natl. Acad. Sci. USA, 2011, 108(4), 1669-1674.
[] [PMID: 21205893]
Zuccato, C.; Tartari, M.; Crotti, A.; Goffredo, D.; Valenza, M.; Conti, L.; Cataudella, T.; Leavitt, B.R.; Hayden, M.R.; Timmusk, T.; Rigamonti, D.; Cattaneo, E. Huntingtin interacts with REST/NRSF to modulate the transcription of NRSE-controlled neuronal genes. Nat. Genet., 2003, 35(1), 76-83.
[] [PMID: 12881722]
Caviston, J.P.; Ross, J.L.; Antony, S.M.; Tokito, M.; Holzbaur, E.L.F. Huntingtin facilitates dynein/dynactin-mediated vesicle transport. Proc. Natl. Acad. Sci. USA, 2007, 104(24), 10045-10050.
[] [PMID: 17548833]
Wu, L.L.; Fan, Y.; Li, S.; Li, X.J.; Zhou, X.F. Huntingtin-associated protein-1 interacts with pro-brain-derived neurotrophic factor and mediates its transport and release. J. Biol. Chem., 2010, 285(8), 5614-5623.
[] [PMID: 19996106]
Gauthier, L.R.; Charrin, B.C.; Borrell-Pagès, M.; Dompierre, J.P.; Rangone, H.; Cordelières, F.P.; De Mey, J.; MacDonald, M.E.; Lessmann, V.; Humbert, S.; Saudou, F. Huntingtin controls neurotrophic support and survival of neurons by enhancing BDNF vesicular transport along microtubules. Cell, 2004, 118(1), 127-138.
[] [PMID: 15242649]
Colin, E.; Zala, D.; Liot, G.; Rangone, H.; Borrell-Pagès, M.; Li, X.J.; Saudou, F.; Humbert, S. Huntingtin phosphorylation acts as a molecular switch for anterograde/retrograde transport in neurons. EMBO J., 2008, 27(15), 2124-2134.
[] [PMID: 18615096]
Zala, D.; Hinckelmann, M.V.; Yu, H.; Lyra da Cunha, M.M.; Liot, G.; Cordelières, F.P.; Marco, S.; Saudou, F. Vesicular glycolysis provides on-board energy for fast axonal transport. Cell, 2013, 152(3), 479-491.
[] [PMID: 23374344]
Parker, J.A.; Metzler, M.; Georgiou, J.; Mage, M.; Roder, J.C.; Rose, A.M.; Hayden, M.R.; Néri, C. Huntingtin-interacting protein 1 influences worm and mouse presynaptic function and protects Caenorhabditis elegans neurons against mutant polyglutamine toxicity. J. Neurosci., 2007, 27(41), 11056-11064.
[] [PMID: 17928447]
Hackam, A.S.; Yassa, A.S.; Singaraja, R.; Metzler, M.; Gutekunst, C.A.; Gan, L.; Warby, S.; Wellington, C.L.; Vaillancourt, J.; Chen, N.; Gervais, F.G.; Raymond, L.; Nicholson, D.W.; Hayden, M.R. Huntingtin interacting protein 1 induces apoptosis via a novel caspase-dependent death effector domain. J. Biol. Chem., 2000, 275(52), 41299-41308.
[] [PMID: 11007801]
Choi, S.A.; Kim, S.J.; Chung, K.C. Huntingtin-interacting protein 1-mediated neuronal cell death occurs through intrinsic apoptotic pathways and mitochondrial alterations. FEBS Lett., 2006, 580(22), 5275-5282.
[] [PMID: 16979168]
Sun, Y.; Savanenin, A.; Reddy, P.H.; Liu, Y.F. Polyglutamine-expanded huntingtin promotes sensitization of N-methyl-D-aspartate receptors via post-synaptic density 95. J. Biol. Chem., 2001, 276(27), 24713-24718.
[] [PMID: 11319238]
Parsons, M.P.; Kang, R.; Buren, C.; Dau, A.; Southwell, A.L.; Doty, C.N.; Sanders, S.S.; Hayden, M.R.; Raymond, L.A. Bidirectional control of postsynaptic density-95 (PSD-95) clustering by huntingtin. J. Biol. Chem., 2014, 289(6), 3518-3528.
[] [PMID: 24347167]
Kim, E.; Cho, K.O.; Rothschild, A.; Sheng, M. Heteromultimerization and NMDA receptor-clustering activity of chapsyn-110, a member of the PSD-95 family of proteins. Neuron, 1996, 17(1), 103-113.
[] [PMID: 8755482]
Garcia, E.P.; Mehta, S.; Blair, L.A.; Wells, D.G.; Shang, J.; Fukushima, T.; Fallon, J.R.; Garner, C.C.; Marshall, J. SAP90 binds and clusters kainate receptors causing incomplete desensitization. Neuron, 1998, 21(4), 727-739.
[] [PMID: 9808460]
Huang, K.; Sanders, S.S.; Kang, R.; Carroll, J.B.; Sutton, L.; Wan, J.; Singaraja, R.; Young, F.B.; Liu, L.; El-Husseini, A.; Davis, N.G.; Hayden, M.R. Wild-type HTT modulates the enzymatic activity of the neuronal palmitoyl transferase HIP14. Hum. Mol. Genet., 2011, 20(17), 3356-3365.
[] [PMID: 21636527]
Yoshii, A.; Murata, Y.; Kim, J.; Zhang, C.; Shokat, K.M.; Constantine-Paton, M. TrkB and protein kinase Mζ regulate synaptic localization of PSD-95 in developing cortex. J. Neurosci., 2011, 31(33), 11894-11904.
[] [PMID: 21849550]
Schaefer, M.H.; Wanker, E.E.; Andrade-Navarro, M.A. Evolution and function of CAG/polyglutamine repeats in protein-protein interaction networks. Nucleic Acids Res., 2012, 40(10), 4273-4287.
[] [PMID: 22287626]
Cattaneo, E.; Zuccato, C.; Tartari, M. Normal huntingtin function: an alternative approach to Huntington’s disease. Nat. Rev. Neurosci., 2005, 6(12), 919-930.
[] [PMID: 16288298]
Zhao, X.; Chen, X.Q.; Han, E.; Hu, Y.; Paik, P.; Ding, Z.; Overman, J.; Lau, A.L.; Shahmoradian, S.H.; Chiu, W.; Thompson, L.M.; Wu, C.; Mobley, W.C. TRiC subunits enhance BDNF axonal transport and rescue striatal atrophy in Huntington’s disease. Proc. Natl. Acad. Sci. USA, 2016, 113(38), E5655-E5664.
[] [PMID: 27601642]
Fornasiero, E.F.; Bonanomi, D.; Benfenati, F.; Valtorta, F. The role of synapsins in neuronal development. Cell. Mol. Life Sci., 2010, 67(9), 1383-1396.
[] [PMID: 20035364]
Shupliakov, O.; Haucke, V.; Pechstein, A. How synapsin I may cluster synaptic vesicles. Semin. Cell Dev. Biol., 2011, 22(4), 393-399.
[] [PMID: 21798362]
Ren, X.; Hurley, J.H. Proline-rich regions and motifs in trafficking: from ESCRT interaction to viral exploitation. Traffic, 2011, 12(10), 1282-1290.
[] [PMID: 21518163]
Xu, Q.; Huang, S.; Song, M.; Wang, C.E.; Yan, S.; Liu, X.; Gaertig, M.A.; Yu, S.P.; Li, H.; Li, S.; Li, X.J. Synaptic mutant huntingtin inhibits synapsin-1 phosphorylation and causes neurological symptoms. J. Cell Biol., 2013, 202(7), 1123-1138.
[] [PMID: 24081492]
Huang, K.; Kang, M.H.; Askew, C.; Kang, R.; Sanders, S.S.; Wan, J.; Davis, N.G.; Hayden, M.R. Palmitoylation and function of glial glutamate transporter-1 is reduced in the YAC128 mouse model of Huntington disease. Neurobiol. Dis., 2010, 40(1), 207-215.
[] [PMID: 20685337]
Milnerwood, A.J.; Gladding, C.M.; Pouladi, M.A.; Kaufman, A.M.; Hines, R.M.; Boyd, J.D.; Ko, R.W.; Vasuta, O.C.; Graham, R.K.; Hayden, M.R.; Murphy, T.H.; Raymond, L.A. Early increase in extrasynaptic NMDA receptor signaling and expression contributes to phenotype onset in Huntington’s disease mice. Neuron, 2010, 65(2), 178-190.
[] [PMID: 20152125]
Bradford, J.; Shin, J.Y.; Roberts, M.; Wang, C.E.; Sheng, G.; Li, S.; Li, X.J. Mutant huntingtin in glial cells exacerbates neurological symptoms of Huntington disease mice. J. Biol. Chem., 2010, 285(14), 10653-10661.
[] [PMID: 20145253]
Chen, L.L.; Wu, J.C.; Wang, L.H.; Wang, J.; Qin, Z.H.; Difiglia, M.; Lin, F. Rapamycin prevents the mutant huntingtin-suppressed GLT-1 expression in cultured astrocytes. Acta Pharmacol. Sin., 2012, 33(3), 385-392.
[] [PMID: 22266730]
Estrada-Sánchez, A.M.; Rebec, G.V. Corticostriatal dysfunction and glutamate transporter 1 (GLT1) in Huntington’s disease: interactions between neurons and astrocytes. Basal Ganglia, 2012, 2(2), 57-66.
[] [PMID: 22905336]
Cui, L.; Jeong, H.; Borovecki, F.; Parkhurst, C.N.; Tanese, N.; Krainc, D. Transcriptional repression of PGC-1alpha by mutant huntingtin leads to mitochondrial dysfunction and neurodegeneration. Cell, 2006, 127(1), 59-69.
[] [PMID: 17018277]
Johri, A.; Starkov, A.A.; Chandra, A.; Hennessey, T.; Sharma, A.; Orobello, S.; Squitieri, F.; Yang, L.; Beal, M.F. Truncated peroxisome proliferator-activated receptor- γ coactivator 1 α splice variant is severely altered inHuntington's disease. Neurodegener. Dis. Neurodegener. Dis., 2011, 8(6), 496-503.
[] [PMID: 21757867]
Kim, J.; Moody, J.P.; Edgerly, C.K.; Bordiuk, O.L.; Cormier, K.; Smith, K.; Beal, M.F.; Ferrante, R.J. Mitochondrial loss, dysfunction and altered dynamics in Huntington’s disease. Hum. Mol. Genet., 2010, 19(20), 3919-3935.
[] [PMID: 20660112]
Poirier, M.A.; Jiang, H.; Ross, C.A. A structure-based analysis of huntingtin mutant polyglutamine aggregation and toxicity: evidence for a compact beta-sheet structure. Hum. Mol. Genet., 2005, 14(6), 765-774.
[] [PMID: 15689354]
Kim, M. Beta conformation of polyglutamine track revealed by a crystal structure of Huntingtin N-terminal region with insertion of three histidine residues. Prion, 2013, 7(3), 221-228.
[] [PMID: 23370273]
Blesa, J.; Phani, S.; Jackson-Lewis, V.; Przedborski, S. Classic and new animal models of Parkinson’s disease. J. Biomed. Biotechnol., 2012, 2012 845618
[] [PMID: 22536024]
Bruijn, L.I.; Miller, T.M.; Cleveland, D.W. Unraveling the mechanisms involved in motor neuron degeneration in ALS. Annu. Rev. Neurosci., 2004, 27, 723-749.
[] [PMID: 15217349]
Rosen, D.R.; Siddique, T.; Patterson, D.; Figlewicz, D.A.; Sapp, P.; Hentati, A.; Donaldson, D.; Goto, J.; O’Regan, J.P.; Deng, H.X. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature, 1993, 362(6415), 59-62.
[] [PMID: 8446170]
Roberts, B.R.; Ryan, T.M.; Bush, A.I.; Masters, C.L.; Duce, J.A. The role of metallobiology and amyloid-β peptides in Alzheimer’s disease. J. Neurochem., 2012, 120(1)(Suppl. 1), 149-166.
[] [PMID: 22121980]
Prusiner, S.B. Molecular biology of prion diseases. Science, 1991, 252(5012), 1515-1522.
[] [PMID: 1675487]
Halliwell, B.; Gutteridge, Free radicals in biology and medicine, ; 3rd ed; Oxford Science Publications, 1999, 226(229), 66.
[ 00]
Maddipati, K.R.; Marnett, L.J. Characterization of the major hydroperoxide-reducing activity of human plasma. Purification and properties of a selenium-dependent glutathione peroxidase. J. Biol. Chem., 1987, 262(36), 17398-17403.
[PMID: 3693360]
Moffitt, W. The Electronic Structure of the Oxygen Molecule Proceedings of the Royal Society of London Series A, 1951, 210(1101), 224-245.
Sas, K.; Robotka, H.; Toldi, J.; Vécsei, L. Mitochondria, metabolic disturbances, oxidative stress and the kynurenine system, with focus on neurodegenerative disorders. J. Neurol. Sci., 2007, 257(1-2), 221-239.
[] [PMID: 17462670]
Wei, Y.H.; Lu, C.Y.; Wei, C.Y.; Ma, Y.S.; Lee, H.C. Oxidative stress in human aging and mitochondrial disease-consequences of defective mitochondrial respiration and impaired antioxidant enzyme system. Chin. J. Physiol., 2001, 44(1), 1-11.
[PMID: 11403514]
Halliwell, B.; Gutteridge, J.M. Role of free radicals and catalytic metal ions in human disease: an overview. Methods Enzymol., 1990, 186, 1-85.
[] [PMID: 2172697]
Gao, H.M.; Liu, B.; Zhang, W.; Hong, J.S. Critical role of microglial NADPH oxidase-derived free radicals in the in vitro MPTP model of Parkinson’s disease. FASEB J., 2003, 17(13), 1954-1956.
[] [PMID: 12897068]
Floyd, R.A. Neuroinflammatory processes are important in neurodegenerative diseases: a hypothesis to explain the increased formation of reactive oxygen and nitrogen species as major factors involved in neurodegenerative disease development. Free Radic. Biol. Med., 1999, 26(9-10), 1346-1355.
[] [PMID: 10381209]
Halliwell, B.; Gutteridge, J.M. Oxygen toxicity, oxygen radicals, transition metals and disease. Biochem. J., 1984, 219(1), 1-14.
[] [PMID: 6326753]
Finkel, T.; Holbrook, N.J. Oxidants, oxidative stress and the biology of ageing. Nature, 2000, 408(6809), 239-247.
[] [PMID: 11089981]
Phaniendra, A.; Jestadi, D.B.; Periyasamy, L. Free radicals: properties, sources, targets, and their implication in various diseases. Indian J. Clin. Biochem., 2015, 30(1), 11-26.
[] [PMID: 25646037]
Gaschler, M.M.; Stockwell, B.R. Lipid peroxidation in cell death. Biochem. Biophys. Res. Commun., 2017, 482(3), 419-425.
[] [PMID: 28212725]
Ciancarelli, I.; De Amicis, D.; Di Massimo, C.; Di Scanno, C.; Pistarini, C.; D’Orazio, N.; Tozzi Ciancarelli, M.G. Peripheral biomarkers of oxidative stress and their limited potential in evaluation of clinical features of Huntington’s patients. Biomarkers, 2014, 19(6), 452-456.
[] [PMID: 24980251]
Klepac, N.; Relja, M.; Klepac, R.; Hećimović, S.; Babić, T.; Trkulja, V. Oxidative stress parameters in plasma of Huntington’s disease patients, asymptomatic Huntington’s disease gene carriers and healthy subjects: a cross-sectional study. J. Neurol., 2007, 254(12), 1676-1683.
[] [PMID: 17990062]
Chen, C.M.; Wu, Y.R.; Cheng, M.L.; Liu, J.L.; Lee, Y.M.; Lee, P.W.; Soong, B.W.; Chiu, D.T. Increased oxidative damage and mitochondrial abnormalities in the peripheral blood of Huntington’s disease patients. Biochem. Biophys. Res. Commun., 2007, 359(2), 335-340.
[] [PMID: 17543886]
Sorolla, M.A.; Rodríguez-Colman, M.J.; Vall-llaura, N.; Tamarit, J.; Ros, J.; Cabiscol, E. Protein oxidation in Huntington disease. Biofactors, 2012, 38(3), 173-185.
[] [PMID: 22473822]
Finkel, T. Radical medicine: treating ageing to cure disease. Nat. Rev. Mol. Cell Biol., 2005, 6(12), 971-976.
[] [PMID: 16227974]
Zecca, L.; Youdim, M.B.; Riederer, P.; Connor, J.R.; Crichton, R.R. Iron, brain ageing and neurodegenerative disorders. Nat. Rev. Neurosci., 2004, 5(11), 863-873.
[] [PMID: 15496864]
Ke, Y.; Qian, Z.M. Brain iron metabolism: neurobiology and neurochemistry. Prog. Neurobiol., 2007, 83(3), 149-173.
[] [PMID: 17870230]
Lovell, M.A.; Robertson, J.D.; Teesdale, W.J.; Campbell, J.L.; Markesbery, W.R. Copper, iron and zinc in Alzheimer’s disease senile plaques. J. Neurol. Sci., 1998, 158(1), 47-52.
[] [PMID: 9667777]
Bishop, G.M.; Robinson, S.R.; Liu, Q.; Perry, G.; Atwood, C.S.; Smith, M.A. Iron: a pathological mediator of Alzheimer disease? Dev. Neurosci., 2002, 24(2-3), 184-187.
[] [PMID: 12401957]
Zatta, P.; Drago, D.; Bolognin, S.; Sensi, S.L. Alzheimer’s disease, metal ions and metal homeostatic therapy. Trends Pharmacol. Sci., 2009, 30(7), 346-355.
[] [PMID: 19540003]
Miller, L.M.; Wang, Q.; Telivala, T.P.; Smith, R.J.; Lanzirotti, A.; Miklossy, J. Synchrotron-based infrared and X-ray imaging shows focalized accumulation of Cu and Zn co-localized with beta-amyloid deposits in Alzheimer’s disease. J. Struct. Biol., 2006, 155(1), 30-37.
[] [PMID: 16325427]
Berg, D. Transcranial ultrasound as a risk marker for Parkinson’s disease. Mov. Disord., 2009, 24(2)(Suppl. 2), S677-S683.
[] [PMID: 19877199]
Gorell, J.M.; Ordidge, R.J.; Brown, G.G.; Deniau, J.C.; Buderer, N.M.; Helpern, J.A. Increased iron-related MRI contrast in the substantia nigra in Parkinson’s disease. Neurology, 1995, 45(6), 1138-1143.
[] [PMID: 7783878]
Ahtoniemi, T.; Goldsteins, G.; Keksa-Goldsteine, V.; Malm, T.; Kanninen, K.; Salminen, A.; Koistinaho, J. Pyrrolidine dithiocarbamate inhibits induction of immunoproteasome and decreases survival in a rat model of amyotrophic lateral sclerosis. Mol. Pharmacol., 2007, 71(1), 30-37.
[] [PMID: 17008387]
Tokuda, E.; Ono, S.; Ishige, K.; Naganuma, A.; Ito, Y.; Suzuki, T. Metallothionein proteins expression, copper and zinc concentrations, and lipid peroxidation level in a rodent model for amyotrophic lateral sclerosis. Toxicology, 2007, 229(1-2), 33-41.
[] [PMID: 17097207]
Nadjar, Y.; Gordon, P.; Corcia, P.; Bensimon, G.; Pieroni, L.; Meininger, V.; Salachas, F. Elevated serum ferritin is associated with reduced survival in amyotrophic lateral sclerosis. PLoS One, 2012, 7(9) e45034
[] [PMID: 23024788]
Bartzokis, G.; Cummings, J.; Perlman, S.; Hance, D.B.; Mintz, J. Increased basal ganglia iron levels in Huntington disease. Arch. Neurol., 1999, 56(5), 569-574.
[] [PMID: 10328252]
Fox, J.H.; Kama, J.A.; Lieberman, G.; Chopra, R.; Dorsey, K.; Chopra, V.; Volitakis, I.; Cherny, R.A.; Bush, A.I.; Hersch, S. Mechanisms of copper ion mediated Huntington’s disease progression. PLoS One, 2007, 2(3) e334
[] [PMID: 17396163]
Fox, J.H.; Connor, T.; Stiles, M.; Kama, J.; Lu, Z.; Dorsey, K.; Lieberman, G.; Sapp, E.; Cherny, R.A.; Banks, M.; Volitakis, I.; DiFiglia, M.; Berezovska, O.; Bush, A.I.; Hersch, S.M. Cysteine oxidation within N-terminal mutant huntingtin promotes oligomerization and delays clearance of soluble protein. J. Biol. Chem., 2011, 286(20), 18320-18330.
[] [PMID: 21454633]
Dashtipour, K.; Liu, M.; Kani, C.; Dalaie, P.; Obenaus, A.; Simmons, D.; Gatto, N.M.; Zarifi, M. Iron accumulation is not homogenous among patients with Parkinson’s Disease. Parkinsons Dis., 2015, 2015 324843
[] [PMID: 25945281]
Bush, A.I. Metals and neuroscience. Curr. Opin. Chem. Biol., 2000, 4(2), 184-191.
[] [PMID: 10742195]
Wang, X.; Michaelis, E.K. Selective neuronal vulnerability to oxidative stress in the brain. Front. Aging Neurosci., 2010, 2, 12.
[] [PMID: 20552050]
Paulson, H.L.; Bonini, N.M.; Roth, K.A. Polyglutamine disease and neuronal cell death. Proc. Natl. Acad. Sci. USA, 2000, 97(24), 12957-12958.
[] [PMID: 11058149]
Goswami, A.; Dikshit, P.; Mishra, A.; Mulherkar, S.; Nukina, N.; Jana, N.R. Oxidative stress promotes mutant huntingtin aggregation and mutant huntingtin-dependent cell death by mimicking proteasomal malfunction. Biochem. Biophys. Res. Commun., 2006, 342(1), 184-190.
[] [PMID: 16472774]
Deckel, A.W.; Tang, V.; Nuttal, D.; Gary, K.; Elder, R. Altered neuronal nitric oxide synthase expression contributes to disease progression in Huntington’s disease transgenic mice. Brain Res., 2002, 939(1-2), 76-86.
[] [PMID: 12020853]
Santamaría, A.; Pérez-Severiano, F.; Rodríguez-Martínez, E.; Maldonado, P.D.; Pedraza-Chaverri, J.; Ríos, C.; Segovia, J. Comparative analysis of superoxide dismutase activity between acute pharmacological models and a transgenic mouse model of Huntington’s disease. Neurochem. Res., 2001, 26(4), 419-424.
[] [PMID: 11495354]
Rebec, G.V.; Barton, S.J.; Ennis, M.D. Dysregulation of ascorbate release in the striatum of behaving mice expressing the Huntington’s disease gene. J. Neurosci., 2002, 22(2), RC202.
[] [PMID: 11784814]
Lee, J.; Kosaras, B.; Del Signore, S.J.; Cormier, K.; McKee, A.; Ratan, R.R.; Kowall, N.W.; Ryu, H. Modulation of lipid peroxidation and mitochondrial function improves neuropathology in Huntington’s disease mice. Acta Neuropathol., 2011, 121(4), 487-498.
[] [PMID: 21161248]
Browne, S.E. Mitochondria and Huntington’s disease pathogenesis: insight from genetic and chemical models. Ann. N. Y. Acad. Sci., 2008, 1147, 358-382.
[] [PMID: 19076457]
Choo, Y.S.; Johnson, G.V.; MacDonald, M.; Detloff, P.J.; Lesort, M. Mutant huntingtin directly increases susceptibility of mitochondria to the calcium-induced permeability transition and cytochrome c release. Hum. Mol. Genet., 2004, 13(14), 1407-1420.
[] [PMID: 15163634]
Hands, S.; Sajjad, M.U.; Newton, M.J.; Wyttenbach, A. In vitro and in vivo aggregation of a fragment of huntingtin protein directly causes free radical production. J. Biol. Chem., 2011, 286(52), 44512-44520.
[] [PMID: 21984825]
Dexter, D.T.; Carayon, A.; Javoy-Agid, F.; Agid, Y.; Wells, F.R.; Daniel, S.E.; Lees, A.J.; Jenner, P.; Marsden, C.D. Alterations in the levels of iron, ferritin and other trace metals in Parkinson’s disease and other neurodegenerative diseases affecting the basal ganglia. Brain, 1991, 114(Pt 4), 1953-1975.
[] [PMID: 1832073]
Hands, S.L.; Mason, R.; Sajjad, M.U.; Giorgini, F.; Wyttenbach, A. Metallothioneins and copper metabolism are candidate therapeutic targets in Huntington’s disease. Biochem. Soc. Trans., 2010, 38(2), 552-558.
[] [PMID: 20298220]
Talarek, S.; Listos, J.; Barreca, D.; Tellone, E.; Sureda, A.; Nabavi, S.F.; Braidy, N.; Nabavi, S.M. Neuroprotective effects of honokiol: from chemistry to medicine. Biofactors, 2017, 43(6), 760-769.
[] [PMID: 28817221]
Barreca, D.; Currò, M.; Bellocco, E.; Ficarra, S.; Laganà, G.; Tellone, E.; Laura Giunta, M.; Visalli, G.; Caccamo, D.; Galtieri, A.; Ientile, R. Neuroprotective effects of phloretin and its glycosylated derivative on rotenone-induced toxicity in human SH-SY5Y neuronal-like cells. Biofactors, 2017, 43(4), 549-557.
[] [PMID: 28401997]
Tellone, E.; Galtieri, A.; Russo, A.; Ficarra, S. Protective effects of the caffeine against neurodegenerative diseases. Curr. Med. Chem., 2019, 26(27), 5137-5151.
[] [PMID: 28990513]
Carelli-Alinovi, C.; Ficarra, S.; Russo, A.M.; Giunta, E.; Barreca, D.; Galtieri, A.; Misiti, F.; Tellone, E. Involvement of acetylcholinesterase and protein kinase C in the protective effect of caffeine against β-amyloid-induced alterations in red blood cells. Biochimie, 2016, 121, 52-59.
[] [PMID: 26620258]
Tellone, E.; Galtieri, A.; Russo, A.; Giardina, B.; Ficarra, S. Resveratrol: a focus on several neurodegenerative diseases. Oxid. Med. Cell. Longev., 2015, 2015 392169
[] [PMID: 26180587]
Tellone, E.; Galtieri, A.; Russo, A.; Ficarra, S. How does resveratrol influence the genesis of some neurodegenerative diseases? Neural Regen. Res., 2016, 11(1), 86-87.
[] [PMID: 26981091]
Rebec, G.V. Dysregulation of corticostriatal ascorbate release and glutamate uptake in transgenic models of Huntington’s disease. Antioxid. Redox Signal., 2013, 19(17), 2115-2128.
[] [PMID: 23642110]
Beal, M.F.; Ferrante, R.J. Experimental therapeutics in transgenic mouse models of Huntington’s disease. Nat. Rev. Neurosci., 2004, 5(5), 373-384.
[] [PMID: 15100720]
Rebec, G.V.; Barton, S.J.; Marseilles, A.M.; Collins, K. Ascorbate treatment attenuates the Huntington behavioral phenotype in mice. Neuroreport, 2003, 14(9), 1263-1265.
[] [PMID: 12824772]
Balazs, Z.; Panzenboeck, U.; Hammer, A.; Sovic, A.; Quehenberger, O.; Malle, E.; Sattler, W. Uptake and transport of high-density lipoprotein (HDL) and HDL-associated alpha-tocopherol by an in vitro blood-brain barrier model. J. Neurochem., 2004, 89(4), 939-950.
[] [PMID: 15140193]
Peyser, C.E.; Folstein, M.; Chase, G.A.; Starkstein, S.; Brandt, J.; Cockrell, J.R.; Bylsma, F.; Coyle, J.T.; McHugh, P.R.; Folstein, S.E. Trial of d-alpha-tocopherol in Huntington’s disease. Am. J. Psychiatry, 1995, 152(12), 1771-1775.
[] [PMID: 8526244]
Miyamoto, M.; Murphy, T.H.; Schnaar, R.L.; Coyle, J.T. Antioxidants protect against glutamate-induced cytotoxicity in a neuronal cell line. J. Pharmacol. Exp. Ther., 1989, 250(3), 1132-1140.
[PMID: 2778712]
Mehrotra, A.; Kanwal, A.; Banerjee, S.K.; Sandhir, R. Mitochondrial modulators in experimental Huntington’s disease: reversal of mitochondrial dysfunctions and cognitive deficits. Neurobiol. Aging, 2015, 36(6), 2186-2200.
[] [PMID: 25976011]
Andreassen, O.A.; Ferrante, R.J.; Dedeoglu, A.; Beal, M.F. Lipoic acid improves survival in transgenic mouse models of Huntington’s disease. Neuroreport, 2001, 12(15), 3371-3373.
[] [PMID: 11711888]
Lu, Z.; Marks, E.; Chen, J.; Moline, J.; Barrows, L.; Raisbeck, M.; Volitakis, I.; Cherny, R.A.; Chopra, V.; Bush, A.I.; Hersch, S.; Fox, J.H. Altered selenium status in Huntington’s disease: neuroprotection by selenite in the N171-82Q mouse model. Neurobiol. Dis., 2014, 71, 34-42.
[] [PMID: 25014023]
Bortolatto, C.F.; Jesse, C.R.; Wilhelm, E.A.; Chagas, P.M.; Nogueira, C.W. Organoselenium bis selenide attenuates 3-nitropropionic acid-induced neurotoxicity in rats. Neurotox. Res., 2013, 23(3), 214-224.
[] [PMID: 22739838]
Hussein, A. A convenient mechanism for the free radical scavenging activity of resveratrol. Int. J. Phytomed., 2011, 3(4), 459-469.
Iuga, C.; Alvarez-Idaboy, J.R.; Russo, N. Antioxidant activity of trans-resveratrol toward hydroxyl and hydroperoxyl radicals: a quantum chemical and computational kinetics study. J. Org. Chem., 2012, 77(8), 3868-3877.
[] [PMID: 22475027]
de Almeida, L.M.; Piñeiro, C.C.; Leite, M.C.; Brolese, G.; Tramontina, F.; Feoli, A.M.; Gottfried, C.; Gonçalves, C.A. Resveratrol increases glutamate uptake, glutathione content and S100B secretion in cortical astrocyte cultures. Cell. Mol. Neurobiol., 2007, 27(5), 661-668.
[] [PMID: 17554623]
Yáñez, M.; Galán, L.; Matías-Guiu, J.; Vela, A.; Guerrero, A.; García, A.G. CSF from amyotrophic lateral sclerosis patients produces glutamate independent death of rat motor brain cortical neurons: protection by resveratrol but not riluzole. Brain Res., 2011, 1423, 77-86.
[] [PMID: 21983205]
Feng, X.; Liang, N.; Zhu, D.; Gao, Q.; Peng, L.; Dong, H.; Yue, Q.; Liu, H.; Bao, L.; Zhang, J.; Hao, J.; Gao, Y.; Yu, X.; Sun, J. Resveratrol inhibits β-amyloid-induced neuronal apoptosis through regulation of SIRT1-ROCK1 signaling pathway. PLoS One, 2013, 8(3) e59888
[] [PMID: 23555824]
Dasgupta, B.; Milbrandt, J. Resveratrol stimulates AMP kinase activity in neurons. Proc. Natl. Acad. Sci. USA, 2007, 104(17), 7217-7222.
[] [PMID: 17438283]
Qian, C.; Jin, J.; Chen, J.; Li, J.; Yu, X.; Mo, H.; Chen, G. SIRT1 activation by resveratrol reduces brain edema and neuronal apoptosis in an experimental rat subarachnoid hemorrhage model. Mol. Med. Rep., 2017, 16(6), 9627-9635.
[] [PMID: 29039533]
Zeidán-Chuliá, F.; Gelain, D.P.; Kolling, E.A.; Rybarczyk-Filho, J.L.; Ambrosi, P.; Terra, S.R.; Pires, A.S.; da Rocha, J.B.; Behr, G.A.; Moreira, J.C. Major components of energy drinks (caffeine, taurine, and guarana) exert cytotoxic effects on human neuronal SH-SY5Y cells by decreasing reactive oxygen species production. Oxid. Med. Cell. Longev., 2013, 2013(6) 791795
[] [PMID: 23766861]
Costa, M.S.; Botton, P.H.; Mioranzza, S.; Ardais, A.P.; Moreira, J.D.; Souza, D.O.; Porciúncula, L.O. Caffeine improves adult mice performance in the object recognition task and increases BDNF and TrkB independent on phospho-CREB immunocontent in the hippocampus. Neurochem. Int., 2008, 53(3-4), 89-94.
[] [PMID: 18620014]
Moy, G.A.; McNay, E.C. Caffeine prevents weight gain and cognitive impairment caused by a high-fat diet while elevating hippocampal BDNF. Physiol. Behav., 2013, 109, 69-74.
[] [PMID: 23220362]
McConell, G.K.; Ng, G.P.; Phillips, M.; Ruan, Z.; Macaulay, S.L.; Wadley, G.D. Central role of nitric oxide synthase in AICAR and caffeine-induced mitochondrial biogenesis in L6 myocytes. J. Appl. Physiol., 2010, 108(3), 589-595.
[] [PMID: 20044477]
Jornayvaz, F.R.; Shulman, G.I. Regulation of mitochondrial biogenesis. Essays Biochem., 2010, 47, 69-84.
[] [PMID: 20533901]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy