Why Is Research on Amyloid‑β Failing to Give New Drugs for Alzheimer’s Disease?

The two hallmarks of Alzheimer’s disease (AD) are the presence of neurofibrillary tangles (NFT) made of aggregates of the hyperphosphorylated tau protein and of amyloid plaques composed of amyloid-β (Aβ) peptides, primarily Aβ1–40 and Aβ1–42. Targeting the production, aggregation, and toxicity of Aβ...

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Bibliographic Details
Published in:ACS chemical neuroscience 2017-07, Vol.8 (7), p.1435-1437
Main Authors: Doig, Andrew J, del Castillo-Frias, Maria P, Berthoumieu, Olivia, Tarus, Bogdan, Nasica-Labouze, Jessica, Sterpone, Fabio, Nguyen, Phuong H, Hooper, Nigel M, Faller, Peter, Derreumaux, Philippe
Format: Article
Language:English
Subjects:
Alzheimer Disease - drug therapy
Alzheimer Disease - metabolism
Amyloid beta-Peptides - metabolism
Animals
Chemical Sciences
Drug Discovery
Humans
Medicinal Chemistry
Neuroprotective Agents - pharmacology
Neuroprotective Agents - therapeutic use
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Summary:The two hallmarks of Alzheimer’s disease (AD) are the presence of neurofibrillary tangles (NFT) made of aggregates of the hyperphosphorylated tau protein and of amyloid plaques composed of amyloid-β (Aβ) peptides, primarily Aβ1–40 and Aβ1–42. Targeting the production, aggregation, and toxicity of Aβ with small molecule drugs or antibodies is an active area of AD research due to the general acceptance of the amyloid cascade hypothesis, but thus far all drugs targeting Aβ have failed. From a review of the recent literature and our own experience based on in vitro, in silico, and in vivo studies, we present some reasons to explain this repetitive failure.
ISSN:1948-7193
1948-7193
DOI:10.1021/acschemneuro.7b00188