The ubiquitin proteasomal system: a potential target for the management of Alzheimer's disease

Journal of Cellular and Molecular Medicine

Volumn 20, Issue 7, 2016, Pages 1392-1407

  Gadhave, Kundlik ^a   Bolshette, Nityanand ^a   Ahire, Ashutosh ^a   Pardeshi, Rohit ^a   Thakur, Krishan ^a   Trandafir, Cristiana ^b   Istrate, Alexandru ^b   Ahmed, Sahabuddin ^a   Lahkar, Mangala ^a   Muresanu, Dafin F ^b,c   Balea, Maria ^b  

^a NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH NIPER   (India)

^b IULIU HATIEGANU UNIVERSITY OF MEDICINE AND PHARMACY   (Romania)

^c RoNeuro Institute for Neurological Research and Diagnostic   (Romania)

Author keywords

Alzheimer's disease; amyloid ; chaperones; ubiquitin

Indexed keywords

5 AMINO 2 (2 FURYL) 7 (2 PHENYLETHYL)PYRAZOLO[4,3 E][1,2,4]TRIAZOLO[1,5 C]PYRIMIDINE; ADS 8704; ASTEMIZOLE; AZD 1080; BAPINEUZUMAB; BEXAROTENE; CEREBROLYSIN; CHAPERONE; CHF 5074; DIMEBON; EPOTHILONE; ESTROGEN; ETAZOLATE; EVP 0962; HOMOTAURINE; HUPERZINE A; INTEPIRDINE; LANSOPRAZOLE; LECOZOTAN; LITHIUM; MIN 5 15; MINOCYCLINE; PF 03654746; PRX 03140; SARACATINIB; SOLANEZUMAB; TD 8954; UBIQUITIN; UNCLASSIFIED DRUG; UNINDEXED DRUG; VALPROIC ACID;

ALZHEIMER DISEASE; AMYOTROPHIC LATERAL SCLEROSIS; DEGENERATIVE DISEASE; GENE MUTATION; GENE TRANSLOCATION; GENETIC SUSCEPTIBILITY; HUMAN; IMMUNOTHERAPY; NERVOUS SYSTEM INFLAMMATION; NONHUMAN; PRIORITY JOURNAL; QUALITY CONTROL; REVIEW; UBIQUITINATION;

EID: 84977520595     PISSN: 15821838     EISSN: None     Source Type: Journal    
DOI: 10.1111/jcmm.12817     Document Type: Review

References (136)

1. Brockwell DJ, Radford SE. Intermediates: ubiquitous species on folding energy landscapes? Curr Opin Struct Biol. 2007; 17: 30–7.
2. Ciechanover A, Kwon YT. Degradation of misfolded proteins in neurodegenerative diseases: therapeutic targets and strategies. Exp Mol Med. 2015; 47: e147.
3. Bukau B, Weissman J, Horwich A. Molecular chaperones and protein quality control. Cell. 2006; 125: 443–51.
4. Zhao Y, Macgurn JA, Liu M, et al. The ART-Rsp5 ubiquitin ligase network comprises a plasma membrane quality control system that protects yeast cells from proteotoxic stress. Elife. 2013; 2: e00459.
5. David CR. The roles of intracellular protein-degradation pathways in neurodegeneration. Nature. 2006; 443: 780–6.
6. Lim J, Yue Z. Neuronal aggregates: formation, clearance, and spreading. Dev Cell. 2015; 32: 491–501.
7. Zheng C, Geetha T, Babu JR. Failure of ubiquitin proteasome system: risk for neurodegenerative diseases. Neurodegener Dis. 2014; 14: 161–75.
8. Koulich E, Li X, DeMartino GN. Relative structural and functional roles of multiple deubiquitylating proteins associated with mammalian 26S proteasome. Mol Biol Cell. 2008; 19: 1072–82.
9. Köhler A, Bajorek M, Groll M, et al. The substrate translocation channel of the proteasome. Biochimie. 2001; 83: 325–32.
10. Alexandra E, Luis S, Manuela LP. The amyloid stretch hypothesis: recruiting proteins toward the dark side. PANAS. 2005; 102: 16672–7.
11. Stadtmueller BM, Hill CP. Proteasome activators. Mol Cell. 2011; 41: 8–19.
12. Upadhya SC, Hegde AN. Role of the ubiquitin proteasome system in Alzheimer's disease. BMC Biochem. 2007; 8 (Suppl. 1): S12.
13. Hong L, Huang HC, Jiang ZF. Relationship between amyloid-beta and the ubiquitin-proteasome system in Alzheimer's disease. Neurol Res. 2014; 36: 276–82.
14. Ristic G, Tsou WL, Todi SV. An optimal ubiquitin-proteasome pathway in the nervous system: the role of deubiquitinating enzymes. Front Mol Neurosci. 2014; 7: 72.
15. Dantuma NP, Bott LC. The ubiquitin-proteasome system in neurodegenerative diseases: precipitating factor, yet part of the solution. Front Mol Neurosci. 2014; 7: 70.
16. Nalepa G, Rolfe M, Harper JW. Drug discovery in the ubiquitin-proteasome system. Nat Rev Drug Discov. 2006; 5: 596–613.
17. Tai H-C, Schuman EM. Ubiquitin, the proteasome and protein degradation in neuronal function and dysfunction. Nat Rev Neurosci. 2008; 9: 826–38.
18. Wang J, Maldonado MA. The ubiquitin-proteasome system and its role in inflammatory and autoimmune diseases. Cell Mol Immunol. 2006; 3: 255–61.
19. Lecker SH, Goldberg AL, Mitch WE. Protein degradation by the ubiquitin-proteasome pathway in normal and disease states. J Am Soc Nephrol. 2006; 17: 1807–19.
20. Xie Y. Structure, assembly and homeostatic regulation of the 26S proteasome. J Mol Cell Biol. 2010; 2: 308–17.
21. Eldridge AG, O'Brien T. Therapeutic strategies within the ubiquitin proteasome system. Cell Death Differ. 2010; 17: 4–13.
22. Morawe T, Hiebel C, Kern A, et al. Protein homeostasis, aging and Alzheimer's disease. Mol Neurobiol. 2012; 46: 41–54.
23. Komander D, Clague MJ, Urbe S. Breaking the chains: structure and function of the deubiquitinases. Nat Rev Mol Cell Biol. 2009; 10: 550–63.
24. Goldberg AL. Protein degradation and protection against misfolded or damaged proteins. Nature. 2003; 426: 895–9.
25. Nguyen LK, Dobrzyński M, Fey D, et al. Polyubiquitin chain assembly and organization determine the dynamics of protein activation and degradation. Front Physiol. 2014; 5: 4.
26. Lehman NL. The ubiquitin proteasome system in neuropathology. Acta Neuropathol. 2009; 118: 329–47.
27. Liu CW, Jacobson AD. Functions of the 19S complex in proteasomal degradation. Trends Biochem Sci. 2013; 38: 103–10.
28. Balakirev MY, Tcherniuk SO, Jaquinod M, et al. Otubains: a new family of cysteine proteases in the ubiquitin pathway. EMBO Rep. 2003; 4: 517–22.
29. da Fonseca PC, Morris EP. Structure of the human 26S proteasome: subunit radial displacements open the gate into the proteolytic core. J Biol Chem. 2008; 283: 23305–14.
30. Keller JN, Hanni KB, Markesbery WR. Impaired proteasome function in Alzheimer's disease. J Neurochem. 2000; 75: 436–9.
31. Wojcik C, DeMartino GN. Intracellular localization of proteasomes. Int J Biochem Cell Biol. 2003; 35: 579–89.
32. Liu C-W, Li X, Thompson D, et al. ATP binding and ATP hydrolysis play distinct roles in the function of 26S proteasome. Mol Cell. 2006; 24: 39–50.
33. Mishto M, Bellavista E, Santoro A, et al. Immunoproteasome and LMP2 polymorphism in aged and Alzheimer's disease brains. Neurobiol Aging. 2006; 27: 54–66.
34. Orre M, Kamphuis W, Dooves S, et al. Reactive glia show increased immunoproteasome activity in Alzheimer's disease. Brain. 2013; 136: 1415–31.
35. Tanaka K. The proteasome: overview of structure and functions. Proc Jpn Acad Ser B Phys Biol Sci. 2009; 85: 12–36.
36. Massaly N, Frances B, Mouledous L. Roles of the ubiquitin proteasome system in the effects of drugs of abuse. Front Mol Neurosci. 2015; 7: 99.
37. Ferrington DA, Gregerson DS. Immunoproteasomes: structure, function, and antigen presentation. Prog Mol Biol Transl Sci. 2012; 109: 75–112.
38. Bar-Nun S, Glickman MH. Proteasomal AAA-ATPases: structure and function. Biochim Biophys Acta. 2012; 1823: 67–82.
39. Bedford L, Paine S, Sheppard PW, et al. Assembly, structure, and function of the 26S proteasome. Trends Cell Biol. 2010; 20: 391–401.
40. Coux O, Tanaka K, Goldberg AL. Structure and functions of the 20S and 26S proteasomes. Annu Rev Biochem. 1996; 65: 801–47.
41. Davies KJ. Degradation of oxidized proteins by the 20S proteasome. Biochimie. 2001; 83: 301–10.
42. Jung T, Grune T. The proteasome and the degradation of oxidized proteins: part I—structure of proteasomes. Redox Biol. 2013; 1: 178–82.
43. Hol EM, van Leeuwen FW, Fischer DF. The proteasome in Alzheimer's disease and Parkinson's disease: lessons from ubiquitin B + 1. Trends Mol Med. 2005; 11: 488–95.
44. Voges D, Zwickl P, Baumeister W. The 26S proteasome: a molecular machine designed for controlled proteolysis. Annu Rev Biochem. 1999; 68: 1015–68.
45. Lee S-H, Moon J-H, Yoon SK, et al. Stable incorporation of ATPase subunits into 19 S regulatory particle of human proteasome requires nucleotide binding and C-terminal tails. J Biol Chem. 2012; 287: 9269–79.
46. Ciechanover A. Intracellular protein degradation: from a vague idea thru the lysosome and the ubiquitin-proteasome system and onto human diseases and drug targeting. Cell Death Differ. 2005; 12: 1178–90.
47. Rabl J, Smith DM, Yu Y, et al. Mechanism of gate opening in the 20S proteasome by the proteasomal ATPases. Mol Cell. 2008; 30: 360–8.
48. Benaroudj N, Zwickl P, Seemüller E, et al. ATP hydrolysis by the proteasome regulatory complex PAN serves multiple functions in protein degradation. Mol Cell. 2003; 11: 69–78.
49. Lu Y, B-h Lee, King RW, et al. Substrate degradation by the proteasome: a single-molecule kinetic analysis. Science. 2015; 348: 1250834.
50. Hegde AN, Upadhya SC. Role of ubiquitin-proteasome-mediated proteolysis in nervous system disease. Biochim Biophys Acta. 2011; 1809: 128–40.
51. Majd S, Power JH, Grantham HJ. Neuronal response in Alzheimer's and Parkinson's disease: the effect of toxic proteins on intracellular pathways. BMC Neurosci. 2015; 16: 69.
52. Rahman M, Zetterberg H, Lendel C, et al. Binding of human proteins to amyloid-beta protofibrils. ACS Chem Biol. 2015; 10: 766–74.
53. Ying Z, Wang H, Wang G. The ubiquitin proteasome system as a potential target for the treatment of neurodegenerative diseases. Curr Pharm Des. 2013; 19: 3305–14.
54. Daniels RW, Miller BR, DiAntonio A. Increased vesicular glutamate transporter expression causes excitotoxic neurodegeneration. Neurobiol Dis. 2011; 41: 415–20.
55. Lau A, Tymianski M. Glutamate receptors, neurotoxicity and neurodegeneration. Pflugers Arch. 2010; 460: 525–42.
56. Johnson DA, Johnson JA. Nrf2-a therapeutic target for the treatment of neurodegenerative diseases. Free Radic Biol Med. 2015; 88: 253–67.
57. Cabezas-Opazo FA, et al. Mitochondrial dysfunction contributes to the pathogenesis of Alzheimer's disease. Oxid Med Cell Longev. 2015; 2015: 509654.
58. Engel PA. Does metabolic failure at the synapse cause Alzheimer's disease? Med Hypotheses. 2014; 83: 802–8.
59. Sensi S. Metal homeostasis in dementia. Free Radic Biol Med. 2014; 75 (Suppl. 1): S9.
60. Hegde AN. The ubiquitin-proteasome pathway and synaptic plasticity. Learn Mem. 2010; 17: 314–27.
61. Naujokat C, Hoffmann S. Role and function of the 26S proteasome in proliferation and apoptosis. Lab Invest. 2002; 82: 965–80.
62. Qing H, Zhou W, Christensen MA, et al. Degradation of BACE by the ubiquitin-proteasome pathway. FASEB J. 2004; 18: 1571–3.
63. Salomone S, Caraci F, Leggio GM, et al. New pharmacological strategies for treatment of Alzheimer's disease: focus on disease modifying drugs. Br J Clin Pharmacol. 2012; 73: 504–17.
64. Aprahamian I, Stella F, Forlenza OV. New treatment strategies for Alzheimer's disease: is there a hope? Indian J Med Res. 2013; 138: 449–60.
65. Gavrilova SI, Kolykhalov IV, Fedorova YB, et al. Possibilities of preventive treatment of Alzheimer's disease: results of the 3-year open prospective comparative study on the efficacy and safety of the course therapy with cerebrolysin and cavinton in elderly patients with the syndrome of mild cognitive impairment. Treatment of neurological and psychiatric diseases. 2010; 110: 62.
66. Fragoso YD, Dantas DC. Cerebrolysin for Alzheimer's disease. Cochrane Database of Systematic Reviews 2002, Issue 3. Art. No.: CD003801.
67. Paul S. Dysfunction of the ubiquitin-proteasome system in multiple disease conditions: therapeutic approaches. BioEssays. 2008; 30: 1172–84.
68. O'Leary JC, Li Q, Marinec P, et al. Phenothiazine-mediated rescue of cognition in tau transgenic mice requires neuroprotection and reduced soluble tau burden. Mol Neurodegener. 2010; 5: article 45.
69. Rochet JC. Novel therapeutic strategies for the treatment of protein-misfolding diseases. Expert Rev Mol Med. 2007; 9: 1–34.
70. Ross C, Poirier M. Protein aggregation and neurodegenerative disease. Nature Med. 2004; 10: S10–7.
71. Upadhya SC, Hegde AN. Ubiquitin-proteasome pathway components as therapeutic targets for CNS maladies. Curr Pharm Des. 2005; 11: 3807–28.
72. Qiutian J, Yulin D, Hong Q. Potential therapeutic strategies for Alzheimer's disease targeting or beyond β-amyloid: insights from clinical trials. BioMed Research International. 2014; 2014: 22.
73. Saraiva A, Cardoso I, Pereira MC, et al. Controlling amyloid-beta peptide (1-42) oligomerization and toxicity by fluorinated nanoparticles. ChemBioChem. 2010; 11: 1905–13.
74. Katherine DL, Kebreten FM, Dexter LL, et al. Treatment with bexarotene, a compound that increases apolipoprotein-E, provides no cognitive benefit in mutant APP/PS1 mice. Mol Neurodegener. 2013; 8: 18.
75. Miners JS, Barua N, Kehoe PG, et al. Aβ-degrading enzymes: potential for treatment of Alzheimer disease. J Neuropathol Exp Neurol. 2011; 70: 944–59.
76. Kumar A, Singh A, Ekavali. A review on Alzheimer's disease pathophysiology and its management: an update. Pharmacol Rep. 2015; 67: 195–203.
77. Edward R, Magdalena T, Michael M, et al. Cerebrolysin decreases amyloid-b production by regulating amyloid protein precursor maturation in a transgenic model of Alzheimer's disease. J Neurosci Res. 2006; 83: 1252–61.
78. Nygaard HB. Current and emerging therapies for Alzheimer's disease. Clin Ther. 2013; 35: 1480–9.
79. Verma R, Peters NR, D'Onofrio M, et al. Ubistatins inhibit proteasome-dependent degradation by binding the ubiquitin chain. Science. 2004; 306: 117–20.
80. Cai Z, Yan LJ. Rapamycin, autophagy, and Alzheimer's disease. J Biochem Pharmacol Res. 2013; 1: 84–90.
81. Nixon RA, Mathews PM, Cataldo AM. The neuronal endosomal-lysosomal system in Alzheimer's disease. J Alzheimers Dis. 2001; 3: 97–107.
82. Butler D, Nixon RA, Bahr BA. Potential compensatory responses through autophagic/lysosomal pathways in neurodegenerative diseases. Autophagy. 2006; 2: 234–7.
83. Yang D-S, Stavrides P, Mohan PS, et al. Reversal of autophagy dysfunction in the TgCRND8 mouse model of Alzheimer's disease ameliorates amyloid pathologies and memory deficits. Brain. 2011; 134: 258–77.
84. Cecarini V, Bonfili L, Cuccioloni M, et al. Crosstalk between the ubiquitin–proteasome system and autophagy in a human cellular model of Alzheimer's disease. Biochim Biophys Acta. 2012; 1822: 1741–51.
85. Lane RF, Shineman DW, Steele JW, et al. Beyond amyloid: the future of therapeutics for Alzheimer's disease. Adv Pharmacol. 2012; 64: 213–71.
86. Boland B, Kumar A, Lee S, et al. Autophagy induction and autophagosome clearance in neurons: relationship to autophagic pathology in Alzheimer's disease. J Neurosci. 2008; 28: 6926–37.
87. Eskelinen E-L, Saftig P. Autophagy: a lysosomal degradation pathway with a central role in health and disease. Biochim Biophys Acta. 2009; 1793: 664–73.
88. Nixon RA. Autophagy, amyloidogenesis and Alzheimer disease. J Cell Sci. 2007; 120: 4081–91.
89. Blair LJ, Sabbagh JJ, Dickey CA. Targeting Hsp90 and its co-chaperones to treat Alzheimer's disease. Expert Opin Ther Tar. 2014; 18: 1219–32.
90. Ou J-R, Tan M-S, Xie A-M, et al. Heat shock protein 90 in Alzheimer's disease. Biomed Res Int. 2014; 2014: 1–7.
91. Salminen A, Ojala J, Kaarniranta K, et al. Hsp90 regulates tau pathology through co-chaperone complexes in Alzheimer's disease. Prog Neurobiol. 2011; 93: 99–110.
92. Takalo M, Haapasalo A, Natunen T, et al. Targeting ubiquilin-1 in Alzheimer's disease. Expert Opin Ther Tar. 2013; 17: 795–810.
93. Wilhelmus MM, De Waal RM, Verbeek MM. Heat shock proteins and amateur chaperones in amyloid-Beta accumulation and clearance in Alzheimer's disease. Mol Neurobiol. 2007; 35: 203–16.
94. Jinwal UK, Koren J, O'Leary JC, et al. Hsp70 ATPase modulators as therapeutics for Alzheimer's and other neurodegenerative diseases. Mol Cell Pharmacol. 2010; 2: 43–6.
95. Gao X, Hu H. Quality control of the proteins associated with neurodegenerative diseases. Acta Biochim Biophys Sin (Shanghai). 2008; 40: 612–8.
96. Bobkova NV, Garbuz DG, Nesterova I, et al. Therapeutic effect of exogenous hsp70 in mouse models of Alzheimer's disease. J Alzheimers Dis. 2014; 38: 425–35.
97. Maiti P, Manna J, Veleri S, et al. Molecular chaperone dysfunction in neurodegenerative diseases and effects of curcumin. Biomed Res Int. 2014; 2014: 495091.
98. Mishra S, Palanivelu K. The effect of curcumin (turmeric) on Alzheimer's disease: an overview. Ann Indian Acad Neurol. 2008; 11: 13.
99. Elliott E, Laufer O, Ginzburg I. BAG-1M is up-regulated in hippocampus of Alzheimers disease patients and associates with tau and APP proteins. J Neurochem. 2009; 109: 1168–78.
100. Elliott E, Tsvetkov P, Ginzburg I. BAG-1 associates with Hsc70· Tau complex and regulates the proteasomal degradation of Tau protein. J Biol Chem. 2007; 282: 37276–84.
101. Carman A, Kishinevsky S, Koren J 3rd, et al. Chaperone-dependent neurodegeneration: a molecular perspective on therapeutic intervention. J Alzheimers Dis Parkinsonism. 2013; 2013: (suppl10). pii:007.
102. Jinwal UK, Trotter JH, Abisambra JF, et al. The Hsp90 kinase co-chaperone Cdc37 regulates tau stability and phosphorylation dynamics. J Biol Chem. 2011; 286: 16976–83.
103. Alves RPS, Yang MJ, Batista MT, et al. Alzheimer's disease: is a vaccine possible? Braz J Med Biol Res. 2014; 47: 438–44.
104. Ubhi K, Rockenstein E, Doppler E, et al. Neurofibrillary and neurodegenerative pathology in APP-transgenic mice injected with AAV2-mutant TAU: neuroprotective effects of Cerebrolysin. Acta Neuropathol. 2009; 117: 699–712.
105. Chouraki V, Seshadri S. Genetics of Alzheimer's disease. Adv Genet. 2014; 87: 245–94.
106. Schulte TW, Neckers LM. The benzoquinone ansamycin 17-allylamino-17-demethoxygeldanamycin binds to HSP90 and shares important biologic activities with geldanamycin. Cancer Chemoth Pharm. 1998; 42: 273–9.
107. Luo W, Dou F, Rodina A, et al. Roles of heat-shock protein 90 in maintaining and facilitating the neurodegenerative phenotype in tauopathies. PNAS. 2007; 104: 9511–6.
108. Manavalan A, Mishra M, Feng L, et al. Brain site-specific proteome changes in aging-related dementia. Exp Mol Med. 2013; 45: e39.
109. Zhang M, Deng Y, Luo Y, et al. Control of BACE1 degradation and APP processing by ubiquitin carboxyl-terminal hydrolase L1. J Neurochem. 2012; 120: 1129–38.
110. Oddo S. The ubiquitin-proteasome system in Alzheimer's disease. J Cell Mol Med. 2008; 12: 363–73.
111. Tai H-C, Serrano-Pozo A, Hashimoto T, et al. The synaptic accumulation of hyperphosphorylated tau oligomers in Alzheimer disease is associated with dysfunction of the ubiquitin-proteasome system. Am J Pathol. 2012; 181: 1426–35.
112. Avila J, Lucas JJ, Perez M, et al. Role of tau protein in both physiological and pathological conditions. Physiol Rev. 2004; 84: 361–84.
113. Dickey CA, Yue M, Lin W-L, et al. Deletion of the ubiquitin ligase CHIP leads to the accumulation, but not the aggregation, of both endogenous phospho-and caspase-3-cleaved tau species. J Neurosci. 2006; 26: 6985–96.
114. Sahara N, Murayama M, Mizoroki T, et al. In vivo evidence of CHIP up-regulation attenuating tau aggregation. J Neurochem. 2005; 94: 1254–63.
115. Casey C, Jeannette NS, Yari C, et al. Acetylation: a new key to unlock tau's role in neurodegeneration. Alzheimers Res Ther. 2014; 6: 29.
116. Galimberti D, Scarpini E. Disease-modifying treatments for Alzheimer's disease. Ther Adv Neurol Disord. 2011; 4: 203–16.
117. Salon ML, Pasquini L, Moreno MB, et al. Relationship between β-amyloid degradation and the 26S proteasome in neural cells. Exp Neurol. 2003; 180: 131–43.
118. Song S, Kim S-Y, Hong Y-M, et al. Essential role of E2-25K/Hip-2 in mediating amyloid-β neurotoxicity. Mol Cell. 2003; 12: 553–63.
119. De Vrij FM, Sluijs JA, Gregori L, et al. Mutant ubiquitin expressed in Alzheimer's disease causes neuronal death1. FASEB J. 2001; 15: 2680–8.
120. Huang Q, Figueiredo-Pereira ME. Ubiquitin/proteasome pathway impairment in neurodegeneration: therapeutic implications. Apoptosis. 2010; 15: 1292–311.
121. Tan Z, Sun X, F-y Hou, et al. Mutant ubiquitin found in Alzheimer's disease causes neuritic beading of mitochondria in association with neuronal degeneration. Cell Death Differ. 2007; 14: 1721–32.
122. Carrard G, Bulteau AL, Petropoulos I, et al. Impairment of proteasome structure and function in aging. Int J Biochem Cell Biol. 2002; 34: 1461–74.
123. Oh S, Hong HS, Hwang E, et al. Amyloid peptide attenuates the proteasome activity in neuronal cells. Mech Ageing Dev. 2005; 126: 1292–9.
124. Mangialasche F, Solomon A, Winblad B, et al. Alzheimer's disease: clinical trials and drug development. Lancet Neurol. 2010; 9: 702–16.
125. Swaminathan A, Jicha GA. Nutrition and prevention of Alzheimer's dementia. Front Aging Neurosci. 2014; 6: 282.
126. Regitz C, Dubling LM, Wenzel U. Amyloid-beta (Aβ (1-42))-induced paralysis in Caenorhabditis elegans is inhibited by the polyphenol quercetin through activation of protein degradation pathways. Mol Nutr Food Res. 2014; 58: 1931–40.
127. Abdel-Salam OM. Stem cell therapy for Alzheimer's disease. CNS Neurol Disord Drug Targets. 2011; 10: 459–85.
128. Schneekloth AR, Pucheault M, Tae HS, et al. Targeted intracellular protein degradation induced by a small molecule: en route to chemical proteomics. Bioorg Med Chem Lett. 2008; 18: 5904–8.
129. Marambaud P, Zhao H, Davies P. Resveratrol promotes clearance of Alzheimer's disease amyloid-β peptides. J Biol Chem. 2005; 280: 37377–82.
130. Huang L, Ho P, Chen CH. Activation and inhibition of the proteasome by betulinic acid and its derivatives. FEBS Lett. 2007; 581: 4955–9.
131. Stanhill A, Haynes CM, Zhang Y, et al. An arsenite-inducible 19S regulatory particle-associated protein adapts proteasomes to proteotoxicity. Mol Cell. 2006; 23: 875–85.
132. Gregori L, Hainfeld JF, Simon MN, et al. Binding of amyloid beta protein to the 20 S proteasome. J Biol Chem. 1997; 272: 58–62.
133. Tseng BP, Green KN, Chan JL, et al. Abeta inhibits the proteasome and enhances amyloid and tau accumulation. Neurobiol Aging. 2008; 29: 1607–18.
134. Wang Y, Mandelkow E. Degradation of tau protein by autophagy and proteasomal pathways. Biochem Soc Trans. 2012; 40: 644–52.
135. Dal Vechio FH, Cerqueira F, Augusto O, et al. Peptides that activate the 20S proteasome by gate opening increased oxidized protein removal and reduced protein aggregation. Free Radic Biol Med. 2014; 67: 304–13.
136. Lee BH, Lee MJ, Park S, et al. Enhancement of proteasome activity by a small-molecule inhibitor of USP14. Nature. 2010; 467: 179–84.