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Current Psychopharmacology


ISSN (Print): 2211-5560
ISSN (Online): 2211-5579

Review Article

Oxidative Stress Targeting Amyloid Beta Accumulation and Clearance in Alzheimer’s Disease: Insight into Pathological Mechanisms and Therapeutic Strategies

Author(s): Sunpreet Kaur, Puneet Kumar and Shamsher Singh*

Volume 9, Issue 1, 2020

Page: [22 - 42] Pages: 21

DOI: 10.2174/2211556009666191231155927


Background: Alzheimer’s disease is the most common neurodegenerative disorder affecting the elderly population and emerges as a leading challenge for the scientific research community. The wide pathological aspects of AD made it a multifactorial disorder and even after long time it’s difficult to treat due to unexplored etiological factors.

Methods: The etiogenesis of AD includes mitochondrial failure, gut dysbiosis, biochemical alterations but deposition of amyloid-beta plaques and neurofibrillary tangles are implicated as major hallmarks of neurodegeneration in AD. The aggregates of these proteins disrupt neuronal signaling, enhance oxidative stress and reduce activity of various cellular enzymes which lead to neurodegeneration in the cerebral cortex, neocortex and hippocampus. The metals like copper, aluminum are involved in APP trafficking and promote amyloidbeta aggregation. Similarly, disturbed ubiquitin proteasomal system, autophagy and amyloid- beta clearance mechanisms exert toxic insult in the brain.

Results and Conclusion: The current review explored the role of oxidative stress in disruption of amyloid homeostasis which further leads to amyloid-beta plaque formation and subsequent neurodegeneration in AD. Presently, management of AD relies on the use of acetylcholinesterase inhibitors, antioxidants and metal chelators but they are not specific measures. Therefore, in this review, we have widely cited the various pathological mechanisms of AD as well as possible therapeutic targets.

Keywords: Alzheimer’s disease, amyloid-beta proteins, insulin-degrading enzymes, oxidative stress, ubiquitin proteasomal system, pathological mechanisms.

Graphical Abstract
Prince M, Bryce R, Albanese E, Wimo A, Ribeiro W, Ferri CP. The global prevalence of dementia: a systematic review and metaanalysis. Alzheimers Dement 2013; 9(1): 63-75.e2.
[] [PMID: 23305823]
Baumgart M, Snyder HM, Carrillo MC, Fazio S, Kim H, Johns H. Summary of the evidence on modifiable risk factors for cognitive decline and dementia: A population-based perspective. Alzheimers Dement 2015; 11(6): 718-26.
[] [PMID: 26045020]
Biasibetti R, Tramontina AC, Costa AP, et al. Green tea (-)epigallocatechin-3-gallate reverses oxidative stress and reduces acetylcholinesterase activity in a streptozotocin-induced model of dementia. Behav Brain Res 2013; 236(1): 186-93.
[] [PMID: 22964138]
Korolev IO. Alzheimer’s disease: a clinical and basic science review. Med Student Res J 2014; 4: 24-33.
Kamat PK, Kalani A, Rai S, Tota SK, Kumar A, Ahmad AS. Streptozotocin intracerebroventricular-induced neurotoxicity and brain insulin resistance: a therapeutic intervention for treatment of sporadic Alzheimer’s disease (sAD)-like pathology. Mol Neurobiol 2016; 53(7): 4548-62.
[] [PMID: 26298663]
Khan MB, Khan MM, Khan A, et al. Naringenin ameliorates Alzheimer’s disease (AD)-type neurodegeneration with cognitive impairment (AD-TNDCI) caused by the intracerebroventricular-streptozotocin in rat model. Neurochem Int 2012; 61(7): 1081-93.
[] [PMID: 22898296]
Spires-Jones TL, Hyman BT. The intersection of amyloid beta and tau at synapses in Alzheimer’s disease. Neuron 2014; 82(4): 756-71.
[] [PMID: 24853936]
Sun X, Chen WD, Wang YD. β-Amyloid: the key peptide in the pathogenesis of Alzheimer’s disease. Front Pharmacol 2015; 6: 221.
[] [PMID: 26483691]
Fu H, Rodriguez GA, Herman M, et al. Tau pathology induces excitatory neuron loss, grid cell dysfunction, and spatial memory deficits reminiscent of early Alzheimer’s disease. Neuron 2017; 93(3): 533-541.e5.
[] [PMID: 28111080]
Wattmo C, Wallin ÅK. Early-versus late-onset Alzheimer disease: long-term functional outcomes, nursing home placement, and risk factors for rate of progression. Dement Geriatr Cogn Disord Extra 2017; 7(1): 172-87.
[] [PMID: 28626471]
Chakrabarti S, Khemka VK, Banerjee A, Chatterjee G, Ganguly A, Biswas A. Metabolic risk factors of sporadic Alzheimer’s disease: implications in the pathology, pathogenesis and treatment. Aging Dis 2015; 6(4): 282-99.
[] [PMID: 26236550]
Wild K, August A, Pietrzik CU, Kins S. Structure and synaptic function of metal binding to the amyloid precursor protein and its proteolytic fragments. Front Mol Neurosci 2017; 10: 21.
[] [PMID: 28197076]
Szabo ST, Harry GJ, Hayden KM, Szabo DT, Birnbaum L. Comparison of metal levels between postmortem brain and ventricular fluid in Alzheimer’s disease and nondemented elderly controls. Toxicol Sci 2016; 150(2): 292-300.
[] [PMID: 26721301]
Rezvanfar MA, Shojaei Saadi HA, Gooshe M, Abdolghaffari AH, Baeeri M, Abdollahi M. Ovarian aging-like phenotype in the hyperandrogenism-induced murine model of polycystic ovary. Oxid Med Cell Longev 2014; 2014: 948951
[] [PMID: 24693338]
Lloret A, Fuchsberger T, Giraldo E, Vina J. Reductive stress: A new concept in Alzheimer’s disease. Curr Alzheimer Res 2016; 13(2): 206-11.
[] [PMID: 26391042]
Joshi YB, Giannopoulos PF, Praticò D. The 12/15-lipoxygenase as an emerging therapeutic target for Alzheimer’s disease. Trends Pharmacol Sci 2015; 36(3): 181-6.
[] [PMID: 25708815]
Ayton S, Lei P, Bush AI. Biometals and their therapeutic implications in Alzheimer’s disease. Neurotherapeutics 2015; 12(1): 109-20.
[] [PMID: 25354461]
Greenough MA, Camakaris J, Bush AI. Metal dyshomeostasis and oxidative stress in Alzheimer’s disease. Neurochem Int 2013; 62(5): 540-55.
[] [PMID: 22982299]
Verdile G, Keane KN, Cruzat VF, et al. Inflammation and oxidative stress: the molecular connectivity between insulin resistance, obesity, and Alzheimer’s disease. Mediators Inflamm 2015; 2015: 105828.
[] [PMID: 26693205]
Wang X, Wang W, Li L, Perry G, Lee HG, Zhu X. Oxidative stress and mitochondrial dysfunction in Alzheimer’s disease. Biochim Biophys Acta 2014; 1842(8): 1240-7.
[] [PMID: 24189435]
Wang J, Gu BJ, Masters CL, Wang YJ. A systemic view of Alzheimer disease - insights from amyloid-β metabolism beyond the brain. Nat Rev Neurol 2017; 13(10): 612-23.
[] [PMID: 28960209]
Morley JE, Farr SA. The role of amyloid-beta in the regulation of memory. Biochem Pharmacol 2014; 88(4): 479-85.
[] [PMID: 24398426]
Keller JN, Hanni KB, Markesbery WR. Impaired proteasome function in Alzheimer’s disease. J Neurochem 2000; 75(1): 436-9.
[] [PMID: 10854289]
Selkoe DJ, Hardy J. The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Mol Med 2016; 8(6): 595-608.
[] [PMID: 27025652]
Penke B, Bogár F, Fülöp L. β-Amyloid and the pathomechanisms of Alzheimer’s disease: a comprehensive view. Molecules 2017; 22(10): 1692.
[] [PMID: 28994715]
Wong BX, Hung YH, Bush AI, Duce JA. Metals and cholesterol: two sides of the same coin in Alzheimer’s disease pathology. Front Aging Neurosci 2014; 6: 91.
[] [PMID: 24860500]
Cheignon C, Tomas M, Bonnefont-Rousselot D, Faller P, Hureau C, Collin F. Oxidative stress and the amyloid beta peptide in Alzheimer’s disease. Redox Biol 2018; 14: 450-64.
[] [PMID: 29080524]
Cristóvão JS, Santos R, Gomes CM. Metals and neuronal metal binding proteins implicated in Alzheimer’s disease. Oxid Med Cell Longev 2016; 2016: 9812178.
[] [PMID: 26881049]
Leong SL, Young TR, Barnham KJ, et al. Quantification of copper binding to amyloid precursor protein domain 2 and its Caenorhabditis elegans ortholog. Implications for biological function. Metallomics 2014; 6(1): 105-16.
[] [PMID: 24276282]
Acevedo KM, Opazo CM, Norrish D, et al. Phosphorylation of amyloid precursor protein at threonine 668 is essential for its copper-responsive trafficking in SH-SY5Y neuroblastoma cells. J Biol Chem 2014; 289(16): 11007-19.
Canu N, Amadoro G, Triaca V, et al. The intersection of NGF/TrkA signaling and amyloid precursor protein processing in Alzheimer’s disease neuropathology. Int J Mol Sci 2017; 18(6): 1319.
[] [PMID: 28632177]
Sastre M, Ritchie CW, Hajji N. Metal ions in Alzheimer’s disease brain. JSM Alzheimers Dis Relat Dement 2015; 2: 1014.
Marr RA, Hafez DM. Amyloid-beta and Alzheimer’s disease: the role of neprilysin-2 in amyloid-beta clearance. Front Aging Neurosci 2014; 6: 187.
[PMID: 25165447]
Zuroff L, Daley D, Black KL, Koronyo-Hamaoui M. Clearance of cerebral Aβ in Alzheimer’s disease: reassessing the role of microglia and monocytes. Cell Mol Life Sci 2017; 74(12): 2167-201.
[] [PMID: 28197669]
Gadhave K, Bolshette N, Ahire A, et al. The ubiquitin proteasomal system: a potential target for the management of Alzheimer’s disease. J Cell Mol Med 2016; 20(7): 1392-407.
[] [PMID: 27028664]
Sweeney P, Park H, Baumann M, et al. Protein misfolding in neurodegenerative diseases: implications and strategies. Transl Neurodegener 2017; 6(1): 6.
[] [PMID: 28293421]
Ganguly G, Chakrabarti S, Chatterjee U, Saso L. Proteinopathy, oxidative stress and mitochondrial dysfunction: cross talk in Alzheimer’s disease and Parkinson’s disease. Drug Des Devel Ther 2017; 11: 797-810.
[] [PMID: 28352155]
Atkin G, Paulson H. Ubiquitin pathways in neurodegenerative disease. Front Mol Neurosci 2014; 7: 63.
[] [PMID: 25071440]
Wang H, Saunders AJ. The role of ubiquitin-proteasome in the metabolism of amyloid precursor protein (APP): implications for novel therapeutic strategies for Alzheimer’s disease. Discov Med 2014; 18(97): 41-50.
[PMID: 25091487]
Vashistha N, Neal SE, Singh A, Carroll SM, Hampton RY. Direct and essential function for Hrd3 in ER-associated degradation. Proceedings of the National Academy of Sciences 201603079.
Saito R, Kaneko M, Kitamura Y, et al. Effects of oxidative stress on the solubility of HRD1, a ubiquitin ligase implicated in Alzheimer’s disease. PLoS One 2014; 9(5)e94576
[] [PMID: 24788773]
Del Prete D, Rice RC, Rajadhyaksha AM, D’Adamio L. Amyloid Precursor Protein (APP) may act as a substrate and a recognition unit for CRL4CRBN and Stub1 E3 ligases facilitating ubiquitination of proteins involved in presynaptic functions and neurodegeneration. J Biol Chem 2016; 291(33): 17209-27.
[] [PMID: 27325702]
Kim C, Yun N, Lee J, et al. Phosphorylation of CHIP at Ser20 by Cdk5 promotes tAIF-mediated neuronal death. Cell Death Differ 2016; 23(2): 333-46.
[] [PMID: 26206088]
Watanabe T, von der Kammer H, Wang X, Shintani Y, Horiguchi T. Neuronal expression of F-box and leucine-rich-repeat protein 2 decreases over Braak stages in the brains of Alzheimer’s disease patients. Neurodegener Dis 2013; 11(1): 1-12.
[] [PMID: 22455980]
Watanabe T, Hikichi Y, Willuweit A, Shintani Y, Horiguchi T. FBL2 regulates amyloid precursor protein (APP) metabolism by promoting ubiquitination-dependent APP degradation and inhibition of APP endocytosis. J Neurosci 2012; 32(10): 3352-65.
[] [PMID: 22399757]
Bobo-Jiménez V, Delgado-Esteban M, Angibaud J, et al. APC/CCdh1-Rock2 pathway controls dendritic integrity and memory. Proceedings of the National Academy of Sciences 201616024.
Miura G. Cell cycle regulation: redox shielding. Nat Chem Biol 2015; 11(9): 632.
Rodriguez-Rodriguez P, Almeida A, Bolaños JP. Brain energy metabolism in glutamate-receptor activation and excitotoxicity: role for APC/C-Cdh1 in the balance glycolysis/pentose phosphate pathway. Neurochem Int 2013; 62(5): 750-6.
[] [PMID: 23416042]
Liu Y, Lü L, Hettinger CL, et al. Ubiquilin-1 protects cells from oxidative stress and ischemic stroke caused tissue injury in mice. J Neurosci 2014; 34(8): 2813-21.
[] [PMID: 24553923]
Pajares M, Jiménez-Moreno N, Dias IHK, et al. Redox control of protein degradation. Redox Biol 2015; 6: 409-20.
[] [PMID: 26381917]
Zare-Shahabadi A, Masliah E, Johnson GV, Rezaei N. Autophagy in Alzheimer’s disease. Rev Neurosci 2015; 26(4): 385-95.
[] [PMID: 25870960]
Tramutola A, Triplett JC, Di Domenico F, et al. Alteration of mTOR signaling occurs early in the progression of Alzheimer disease (AD): analysis of brain from subjects with pre-clinical AD, amnestic mild cognitive impairment and late-stage AD. J Neurochem 2015; 133(5): 739-49.
[] [PMID: 25645581]
Meijer AJ, Lorin S, Blommaart EF, Codogno P. Regulation of autophagy by amino acids and MTOR-dependent signal transduction. Amino Acids 2015; 47(10): 2037-63.
[] [PMID: 24880909]
Tan PL, Shavlakadze T, Grounds MD, Arthur PG. Differential thiol oxidation of the signaling proteins Akt, PTEN or PP2A determines whether Akt phosphorylation is enhanced or inhibited by oxidative stress in C2C12 myotubes derived from skeletal muscle. Int J Biochem Cell Biol 2015; 62: 72-9.
[] [PMID: 25737250]
Morris DH, Yip CK, Shi Y, Chait BT, Wang QJ. Beclin 1-Vps34 complex architecture: understanding the nuts and bolts of therapeutic targets. Front Biol (Beijing) 2015; 10(5): 398-426.
[] [PMID: 26692106]
Pattingre S. The antiapoptotic protein BCL-2 has also an antiautophagy role through beclin 1 inhibition. In: Hayat MA, Ed. Autophagy: cancer, other pathologies, inflammation, immunity, infection, and aging. The Netherlands: Elsevier 2016; pp. 165-74.
Zhou YY, Li Y, Jiang WQ, Zhou LF. MAPK/JNK signalling: a potential autophagy regulation pathway. Biosci Rep 2015; 35(3)e00199
[] [PMID: 26182361]
Filomeni G, De Zio D, Cecconi F. Oxidative stress and autophagy: the clash between damage and metabolic needs. Cell Death Differ 2015; 22(3): 377-88.
[] [PMID: 25257172]
Wauson EM, Dbouk HA, Ghosh AB, Cobb MH. G protein-coupled receptors and the regulation of autophagy. Trends Endocrinol Metab 2014; 25(5): 274-82.
[] [PMID: 24751357]
Suwanjang W, Abramov AY, Govitrapong P, Chetsawang B. Melatonin attenuates dexamethasone toxicity-induced oxidative stress, calpain and caspase activation in human neuroblastoma SH-SY5Y cells. J Steroid Biochem Mol Biol 2013; 138: 116-22.
[] [PMID: 23688838]
Sagare AP, Bell RD, Zlokovic BV. Neurovascular defects and faulty amyloid-β vascular clearance in Alzheimer’s disease. J Alzheimers Dis 2013; 33(s1)(Suppl. 1): S87-S100.
[] [PMID: 22751174]
Rufino-Ramos D, Albuquerque PR, Carmona V, Perfeito R, Nobre RJ, Pereira de Almeida L. Extracellular vesicles: Novel promising delivery systems for therapy of brain diseases. J Control Release 2017; 262: 247-58.
[] [PMID: 28687495]
Bien-Ly N, Boswell CA, Jeet S, et al. Lack of widespread BBB disruption in Alzheimer’s disease models: focus on therapeutic antibodies. Neuron 2015; 88(2): 289-97.
[] [PMID: 26494278]
Montagne A, Barnes SR, Sweeney MD, et al. Blood-brain barrier breakdown in the aging human hippocampus. Neuron 2015; 85(2): 296-302.
[] [PMID: 25611508]
Storck SE, Meister S, Nahrath J, et al. Endothelial LRP1 transports amyloid-β(1-42) across the blood-brain barrier. J Clin Invest 2016; 126(1): 123-36.
[] [PMID: 26619118]
Wan W, Cao L, Liu L, et al. Aβ(1-42) oligomer-induced leakage in an in vitro blood-brain barrier model is associated with up-regulation of RAGE and metalloproteinases, and down-regulation of tight junction scaffold proteins. J Neurochem 2015; 134(2): 382-93.
[] [PMID: 25866188]
Chen S, Yin L, Xu Z, et al. Inhibiting receptor for advanced glycation end product (AGE) and oxidative stress involved in the protective effect mediated by glucagon-like peptide-1 receptor on AGE induced neuronal apoptosis. Neurosci Lett 2016; 612: 193-8.
[] [PMID: 26679229]
Zenaro E, Piacentino G, Constantin G. The blood-brain barrier in Alzheimer’s disease. Neurobiol Dis 2017; 107: 41-56.
[] [PMID: 27425887]
Winkler EA, Sagare AP, Zlokovic BV. The pericyte: a forgotten cell type with important implications for Alzheimer’s disease? Brain Pathol 2014; 24(4): 371-86.
[] [PMID: 24946075]
Kisler K, Nelson AR, Rege SV, et al. Pericyte degeneration leads to neurovascular uncoupling and limits oxygen supply to brain. Nat Neurosci 2017; 20(3): 406-16.
[] [PMID: 28135240]
Rustenhoven J, Jansson D, Smyth LC, Dragunow M. Brain pericytes as mediators of neuroinflammation. Trends Pharmacol Sci 2017; 38(3): 291-304.
[] [PMID: 28017362]
Halliday MR, Rege SV, Ma Q, et al. Accelerated pericyte degeneration and blood-brain barrier breakdown in apolipoprotein E4 carriers with Alzheimer’s disease. J Cereb Blood Flow Metab 2016; 36(1): 216-27.
[] [PMID: 25757756]
Tai LM, Thomas R, Marottoli FM, et al. The role of APOE in cerebrovascular dysfunction. Acta Neuropathol 2016; 131(5): 709-23.
[] [PMID: 26884068]
Teng Z, Guo Z, Zhong J, et al. ApoE Influences the Blood-brain barrier through the NF-κB/MMP-9 pathway after traumatic brain injury. Sci Rep 2017; 7(1): 6649.
[] [PMID: 28751738]
Zhang L, Bahety P, Ee PLR. Wnt co-receptor LRP5/6 overexpression confers protection against hydrogen peroxide-induced neurotoxicity and reduces tau phosphorylation in SH-SY5Y cells. Neurochem Int 2015; 87: 13-21.
[] [PMID: 25959626]
Siegenthaler JA, Sohet F, Daneman R. ‘Sealing off the CNS’: cellular and molecular regulation of blood-brain barriergenesis. Curr Opin Neurobiol 2013; 23(6): 1057-64.
[] [PMID: 23867075]
Deng S, Liu H, Qiu K, You H, Lei Q, and Lu W. Role of the Golgi apparatus in the blood - brain barrier: golgi protection may be a targeted therapy for neurological diseases. Mol Neurobiol 2018; 55(6): 4788-801.
[] [PMID: 28730529]
Lan YL, Zou S, Chen JJ, Zhao J, Li S. The neuroprotective effect of the association of aquaporin-4/glutamate transporter-1 against Alzheimer’s disease. Neural Plast 2016; 20164626593
[] [PMID: 27057365]
Xiao Q, Chen Z, Jin X, Mao R, Chen Z. The many postures of noncanonical Wnt signaling in development and diseases. Biomed Pharmacother 2017; 93: 359-69.
[] [PMID: 28651237]
Bronzuoli MR, Iacomino A, Steardo L, Scuderi C. Targeting neuroinflammation in Alzheimer’s disease. J Inflamm Res 2016; 9: 199-208.
[] [PMID: 27843334]
Wang WY, Tan MS, Yu JT, Tan L. Role of pro-inflammatory cytokines released from microglia in Alzheimer’s disease. Ann Transl Med 2015; 3(10): 136.
[PMID: 26207229]
Patterson SL. Immune dysregulation and cognitive vulnerability in the aging brain: interactions of microglia, IL-1β, BDNF and synaptic plasticity. Neuropharmacology 2015; 96(Pt A): 11-8.
[] [PMID: 25549562]
Orihuela R, McPherson CA, Harry GJ. Microglial M1/M2 polarization and metabolic states. Br J Pharmacol 2016; 173(4): 649-65.
[] [PMID: 25800044]
Ransohoff RM. A polarizing question: do M1 and M2 microglia exist? Nat Neurosci 2016; 19(8): 987-91.
[] [PMID: 27459405]
Cherry JD, Olschowka JA, O’Banion MK. Neuroinflammation and M2 microglia: the good, the bad, and the inflamed. J Neuroinflammation 2014; 11(1): 98.
[] [PMID: 24889886]
Zhao X, Sun G, Ting SM, et al. Cleaning up after ICH: the role of Nrf2 in modulating microglia function and hematoma clearance. J Neurochem 2015; 133(1): 144-52.
[] [PMID: 25328080]
Colonna M, Wang Y. TREM2 variants: new keys to decipher Alzheimer disease pathogenesis. Nat Rev Neurosci 2016; 17(4): 201-7.
[] [PMID: 26911435]
Ries M, Sastre M. Mechanisms of Aβ clearance and degradation by glial cells. Front Aging Neurosci 2016; 8: 160.
[] [PMID: 27458370]
Nalivaeva NN, Belyaev ND, Kerridge C, Turner AJ. Amyloid-clearing proteins and their epigenetic regulation as a therapeutic target in Alzheimer’s disease. Front Aging Neurosci 2014; 6: 235.
[] [PMID: 25278875]
Brkic M, Balusu S, Libert C, Vandenbroucke RE. Friends or foes: matrix metalloproteinases and their multifaceted roles in neurodegenerative diseases. Mediators Inflamm 2015; 2015: 620581.
[] [PMID: 26538832]
Chen PT, Chen CL, Lin LTW, et al. Design of peptide substrate for sensitively and specifically detecting two Aβ-degrading enzymes: neprilysin and angiotensin-converting enzyme. PLoS One 2016; 11(4)e0153360
[] [PMID: 27096746]
McCord LA, Liang WG, Dowdell E, et al. Conformational states and recognition of amyloidogenic peptides of human insulin-degrading enzyme. Proc Natl Acad Sci USA 2013; 110(34): 13827-32.
[] [PMID: 23922390]
Abdul-Hay SO, Bannister TD, Wang H, et al. Selective targeting of extracellular insulin-degrading enzyme by quasi-irreversible thiol-modifying inhibitors. ACS Chem Biol 2015; 10(12): 2716-24.
[] [PMID: 26398879]
Kochkina EG, Plesneva SA, Vasilev DS, Zhuravin IA, Turner AJ, Nalivaeva NN. Effects of ageing and experimental diabetes on insulin-degrading enzyme expression in male rat tissues. Biogerontology 2015; 16(4): 473-84.
[] [PMID: 25792373]
Hubin E, Cioffi F, Rozenski J, van Nuland NA, Broersen K. Characterization of insulin-degrading enzyme-mediated cleavage of Aβ in distinct aggregation states. Biochim Biophys Acta 2016; 1860(6): 1281-90.
[] [PMID: 26968463]
Li X, Li N, Sun HL, et al. Maternal lead exposure induces down-regulation of hippocampal insulin-degrading enzyme and nerve growth factor expression in mouse pups. Biomed Environ Sci 2017; 30(3): 215-9.
[PMID: 28427492]
Grasso G, Salomone F, Tundo GR, et al. Metal ions affect insulin-degrading enzyme activity. J Inorg Biochem 2012; 117: 351-8.
[] [PMID: 22819648]
Yui D, Nishida Y, Nishina T, et al. Enhanced phospholipase A2 group 3 expression by oxidative stress decreases the insulin-degrading enzyme. PLoS One 2015; 10(12)e0143518
[] [PMID: 26637123]
Pivovarova O, Höhn A, Grune T, Pfeiffer AF, Rudovich N. Insulin-degrading enzyme: new therapeutic target for diabetes and Alzheimer’s disease? Ann Med 2016; 48(8): 614-24.
[] [PMID: 27320287]
Dineley KT, Jahrling JB, Denner L. Insulin resistance in Alzheimer’s disease. Neurobiol Dis 2014; 72(Pt A): 92-103.
[] [PMID: 25237037]
Koriyama Y, Furukawa A. S-Nitrosylation regulates cell survival and death in the central nervous system. Neurochem Res 2018; 43(1): 50-8.
[] [PMID: 28523529]
Akhtar MW, Sanz-Blasco S, Dolatabadi N, et al. Elevated glucose and oligomeric β-amyloid disrupt synapses via a common pathway of aberrant protein S-nitrosylation. Nat Commun 2016; 7: 10242.
[] [PMID: 26743041]
Tundo GR, Sbardella D, Ciaccio C, et al. Multiple functions of insulin-degrading enzyme: a metabolic crosslight? Crit Rev Biochem Mol Biol 2017; 52(5): 554-82.
[] [PMID: 28635330]
Wang XX, Tan MS, Yu JT, Tan L. Matrix metalloproteinases and their multiple roles in Alzheimer’s disease.BioMed Res Int 2014; 2014: 908636.
[] [PMID: 25050378]
Lakhan SE, Kirchgessner A, Tepper D, Leonard A. Matrix metalloproteinases and blood-brain barrier disruption in acute ischemic stroke. Front Neurol 2013; 4: 32.
[] [PMID: 23565108]
Rogeberg M, Furlund CB, Moe MK, Fladby T. Identification of peptide products from enzymatic degradation of amyloid beta. Biochimie 2014; 105: 216-20.
[] [PMID: 25010651]
Kaminari A, Giannakas N, Tzinia A, Tsilibary EC. Overexpression of matrix metalloproteinase-9 (MMP-9) rescues insulin-mediated impairment in the 5XFAD model of Alzheimer’s disease. Sci Rep 2017; 7(1): 683-95.
[] [PMID: 28386117]
Hussein MZA. Serum matrix metalloproteinase 3 and tissue inhibitor metalloproteinase 1 in vascular dementia: a comparative study. Adv Aging Res 2015; 4(05): 154-69.
Hernandez-Guillamon M, Mawhirt S, Blais S, et al. Sequential Abeta degradation by the matrix metalloproteases MMP-2 and MMP-9. J Biol Chem 2015; 290(24): 15078-91.
Mlekusch R, Humpel C. Matrix metalloproteinases-2 and -3 are reduced in cerebrospinal fluid with low beta-amyloid1-42 levels. Neurosci Lett 2009; 466(3): 135-8.
[] [PMID: 19786072]
Chang X, Rong C, Chen Y, et al. (-)-Epigallocatechin-3-gallate attenuates cognitive deterioration in Alzheimer’s disease model mice by upregulating neprilysin expression. Exp Cell Res 2015; 334(1): 136-45.
[] [PMID: 25882496]
Grimm MO, Mett J, Stahlmann CP, Haupenthal VJ, Zimmer VC, Hartmann T. Neprilysin and Aβ clearance: impact of the APP intracellular domain in NEP regulation and implications in Alzheimer’s disease. Front Aging Neurosci 2013; 5: 98.
[] [PMID: 24391587]
Chen PT, Chen ZT, Hou WC, Yu LC, Chen RP. Polyhydroxycurcuminoids but not curcumin upregulate neprilysin and can be applied to the prevention of Alzheimer’s disease. Sci Rep 2016; 6: 29760-74.
[] [PMID: 27407064]
Nalivaeva NN, Belyaev ND, Zhuravin IA, Turner AJ. The Alzheimer’s amyloid-degrading peptidase, neprilysin: can we control it? Int J Alzheimers Dis 2012; 2012: 383796.
[] [PMID: 22900228]
Kenche VB, Barnham KJ. Alzheimer’s disease & metals: therapeutic opportunities. Br J Pharmacol 2011; 163(2): 211-9.
[] [PMID: 21232050]
Ferreira-Vieira TH, Guimaraes IM, Silva FR, Ribeiro FM. Alzheimer’s disease: targeting the cholinergic system. Curr Neuropharmacol 2016; 14(1): 101-15.
[] [PMID: 26813123]
Korshavn KJ, Jang M, Kwak YJ, et al. Reactivity of metal-free and metal-associated amyloid-β with glycosylated polyphenols and their esterified derivatives. Sci Rep 2015; 5: 17842-51.
[] [PMID: 26657338]
Drew SC. The case for abandoning therapeutic chelation of copper ions in Alzheimer’s disease. Front Neurosci 2017; 11: 317.
[] [PMID: 28626387]
Faux NG, Ritchie CW, Gunn A, et al. PBT2 rapidly improves cognition in Alzheimer’s Disease: additional phase II analyses. J Alzheimers Dis 2010; 20(2): 509-16.
[] [PMID: 20164561]
Solanki I, Parihar P, Mansuri ML, Parihar MS. Flavonoid-based therapies in the early management of neurodegenerative diseases. Adv Nutr 2015; 6(1): 64-72.
[] [PMID: 25593144]
Sarkar J, Nandy SK, Chowdhury A, Chakraborti T, Chakraborti S. Inhibition of MMP-9 by green tea catechins and prediction of their interaction by molecular docking analysis. Biomed Pharmacother 2016; 84: 340-7.
[] [PMID: 27668533]
Apetz N, Munch G, Govindaraghavan S, Gyengesi E. Natural compounds and plant extracts as therapeutics against chronic inflammation in Alzheimer’s disease-a translational perspective. CNS & Neurological Disorders-Drug Targets (Formerly. Curr Drug Targets CNS Neurol Disord 2014; 13(7): 1175-91.
[] [PMID: 25230232]
Pandey AK, Bhattacharya P, Shukla SC, Paul S, Patnaik R. Resveratrol inhibits matrix metalloproteinases to attenuate neuronal damage in cerebral ischemia: a molecular docking study exploring possible neuroprotection. Neural Regen Res 2015; 10(4): 568-75.
[] [PMID: 26170816]

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