Cited by 1,965Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Amyloid Beta: Structure, Biology and Structure-Based Therapeutic Development

Open access
Chen, Guo-fang, Xu, Ting-hai, Yan, Yan, Zhou, Yu-ren, Jiang, Yi, Melcher, Karsten, Xu, H Eric·2017·Acta Pharmacologica Sinica

Abstract

Amyloid beta peptide (Aβ) is produced through the proteolytic processing of a transmembrane protein, amyloid precursor protein (APP), by β- and γ-secretases. Aβ accumulation in the brain is proposed to be an early toxic event in the pathogenesis of Alzheimer's disease, which is the most common form of dementia associated with plaques and tangles in the brain. Currently, it is unclear what the physiological and pathological forms of Aβ are and by what mechanism Aβ causes dementia. Moreover, there are no efficient drugs to stop or reverse the progression of Alzheimer's disease. In this paper, we review the structures, biological functions, and neurotoxicity role of Aβ. We also discuss the potential receptors that interact with Aβ and mediate Aβ intake, clearance, and metabolism. Additionally, we summarize the therapeutic developments and recent advances of different strategies for treating Alzheimer's disease. Finally, we will report on the progress in searching for novel, potentially effective agents as well as selected promising strategies for the treatment of Alzheimer's disease. These prospects include agents acting on Aβ, its receptors and tau protein, such as small molecules, vaccines and antibodies against Aβ; inhibitors or modulators of β- and γ-secretase; Aβ-degrading proteases; tau protein inhibitors and vaccines; amyloid dyes and microRNAs.

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Crossref · 10.1038/aps.2017.28

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  • Aggregation of Aβ1-42 monomers first gives rise to soluble oligomeric species, which further assemble to form insoluble fibrils accumulating in brain parenchyma and other tissues.

    “The aggregation of Aβ1-42 monomers first gives rise to soluble oligomeric species, which further assemble to form insoluble aggregates known as fibrils accumulating in the brain parenchyma and other tissues (Chen et al., 2017).”

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  1. Vannostrand WE, Rozemuller AJM, Chung R, Cotman CW, Saporitoirwin SM. Amyloid beta-protein precursor in cultured leptomeningeal smooth-muscle cells. Amyloid-Int J Exp Clin Invest 1994; 1: 1-7.
  2. Walsh DM, Lomakin A, Benedek GB, Condron MM, Teplow DB. Amyloid beta-protein fibrillogenesis. Detection of a protofibrillar intermediate. J Biol Chem 1997; 272: 22364-72.
  3. Zhang S, Iwata K, Lachenmann MJ, Peng JW, Li S, Stimson ER, et al. The Alzheimer's peptide a beta adopts a collapsed coil structure in water. J Struct Biol 2000; 130: 130-41.
  4. Rozemuller A, Awan T, Ghetti B, Puoti G, Eikelenboom P, Tagliavini F. Microglia and complement in the cortex of Creutzfeldt-Jakob disease and comparison with Alzheimer's disease. Brain Pathol 2000; 10: 658. 134
  5. Hardy J, Selkoe DJ. Medicine-the amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 2002; 297: 353-6. 167
  6. Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer's disease: Progress and problems on the road to therapeutics. Science 2002; 297: 353-6. 176
  7. Zlokovic BV, Deane R, Sallstrom J, Chow N, Miano JM. Neurovascular pathways and Alzheimer amyloid beta-peptide. Brain Pathol 2005; 15: 78-83. 180
  8. Mayeux R, Tang MX, Jacobs DM, Manly J, Bell K, Merchant C, et al. Plasma amyloid beta-peptide 1-42 and incipient Alzheimer's disease. Ann Neurol 1999; 46: 412-6. 181
  9. DeMattos RB, Bales KR, Cummins DJ, Dodart JC, Paul SM, Holtzman DM. Peripheral anti-A beta antibody alters CNS and plasma A beta clearance and decreases brain A beta burden in a mouse model of Alzheimer's disease. Proc Natl Acad Sci U S A 2001; 98: 8850-5. 183
  10. Deane R, Du Yan S, Submamaryan RK, LaRue B, Jovanovic S, Hogg E, et al. RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain. Nat Med 2003; 9: 907-13. 187
  11. Shibata M, Yamada S, Kumar SR, Calero M, Bading J, Frangione B, et al. Clearance of Alzheimer's amyloid-beta1-40 peptide from brain by LDL receptor-related protein-1 at the blood-brain barrier. J Clin Invest 2000; 106: 1489-99. 192
  12. Strittmatter WJ, Saunders AM, Schmechel D, Pericak-Vance M, Enghild J, Salvesen GS, et al. Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late- onset familial Alzheimer disease. Proc Natl Acad Sci U S A 1993; 90: 1977-81. 224
  13. Bryson HM, Benfield P. Donepezil. Drug Aging 1997; 10: 234-9. 257
  14. Granic I, Nyakas C, Luiten PG, Eisel UL, Halmy LG, Gross G, et al. Calpain inhibition prevents amyloid-beta-induced neurodegeneration and associated behavioral dysfunction in rats. Neuropharmacology 2010; 59: 334-42. 273
  15. L a n n fe l t L , Re l k i n N R , S i e m e r s E R . A my l o i d -s s -d i r e c te d immunotherapy for Alzheimer's disease. J Int Med 2014; 275: 284- 95. 286
  16. Mueller-Steiner S, Zhou Y, Arai H, Roberson ED, Sun BG, Chen J, et al. Antiamyloidogenic and neuroprotective functions of cathepsin B: implications for Alzheimer's disease. Neuron 2006; 51: 703-14. 314
  17. Godyn J, Jonczyk J, Panek D, Malawska B. Therapeutic strategies for Alzheimer's disease in clinical trials. Pharmacol Rep 2016; 68: 127-38. 318
  18. Soto C, Sigurdsson EM, Morelli L, Kumar RA, Castano EM, Frangione B. Beta-sheet breaker peptides inhibit fibrillogenesis in a rat brain model of amyloidosis: implications for Alzheimer's therapy. Nat Med 1998; 4: 822-6. 321
  19. Lopez-Miranda V, Soto-Montenegro ML, Vera G, Herradon E, Desco M, Abalo R. Resveratrol: a neuroprotective polyphenol in the Mediterranean diet. Rev Neurol 2012; 54: 349-56. 352
  20. Tucker HM, Kihiko-Ehmann M, Wright S, Rydel RE, Estus S. Tissue plasminogen activator requires plasminogen to modulate amyloid- beta neurotoxicity and deposition. J Neurochem 2000; 75: 2172-7. 356
  21. Yamin R, Bagchi S, Hildebrant R, Scaloni A, Widom RL, Abraham CR. Acyl peptide hydrolase, a serine proteinase isolated from conditioned medium of neuroblastoma cells, degrades the amyloid-beta peptide. J Neurochem 2007; 100: 458-67. 357
  22. Yamin R, Zhao C, O'Connor PB, McKee AC, Abraham CR. Acyl peptide hydrolase degrades monomeric and oligomeric amyloid-beta peptide. Mol Neurodegener 2009; 4: 33. 358

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Authors
Chen, G.-F., Xu, T.-H., Yan, Y., Zhou, Y.-R., Jiang, Y., Melcher, K., & Xu, H. E.
Affiliations
  • Chinese Academy of Sciences (CN)
  • Van Andel Institute (US)
Corresponding author
  • Chen, Guo-fang
  • Xu, H Eric
Venue
Acta Pharmacologica Sinica
Published
2017-07-17
Volume
38
Issue
9
Pages
1205-1235
ISSN
  • 0253-9756 (ISSN-L)
  • 1671-4083
  • 1745-7254
OpenAlex
W2734651019
Cited by
1,965
References
345
Citations by year
2026: 202 · 2025: 338 · 2024: 335 · 2023: 318 · 2022: 293 · 2021: 253 · 2020: 155 · 2019: 52 · 2018: 15 · 2017: 2
FWCI
7.52
Type
journal article
Language
en
Open access
Locations
  • Acta Pharmacologica Sinica (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China (31300607)
  • Science and Technology Commission of Shanghai Municipality (13ZR1447600)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
amyloid-beta, Alzheimer's disease, amyloid precursor protein, beta-secretase, gamma-secretase, amyloid plaques, neurotoxicity, amyloid-beta clearance, structure-based drug design, secretase inhibitors, tau protein, anti-amyloid antibodies, microRNA
MeSH terms
Alzheimer Disease, Animals, Antibodies, Humans, Protein Conformation, Vaccines, Amyloid beta-Peptides, Small Molecule Libraries

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