Amyloid Beta: Structure, Biology and Structure-Based Therapeutic Development
Open accessAbstract
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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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).”
From Exploring the Therapeutic Potential of Phytochemicals in Alzheimer’s Disease: Focus on Polyphenols and Monoterpenes (2022) · cites this paper as Chen et al., 2017
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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
- PMC
- PMC5589967
- 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
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- 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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