TY - JOUR
T1 - Why Is Research on Amyloid-ß Failing to Give New Drugs for Alzheimer’s Disease?
AU - Doig, Andrew
AU - Del Castillo Frias, Maria
AU - Berthoumieu, Olivia
AU - Tarus, Bogdan
AU - Nasica-Labouze, Jessica
AU - Sterpone, Fabio
AU - Nguyen, Phuong H
AU - Hooper, Nigel M
AU - Faller, Peter
AU - Derreumaux, Philippe
PY - 2017/7/19
Y1 - 2017/7/19
N2 - 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 A 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.
AB - 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 A 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.
KW - amyloid-β
KW - Alzheimer’s disease
KW - in vitro and in vivo studies
KW - Computer simulations
KW - drugs
U2 - 10.1021/acschemneuro.7b00188
DO - 10.1021/acschemneuro.7b00188
M3 - Article
VL - 8
SP - 1435
EP - 1437
JO - ACS Chemical Neuroscience
JF - ACS Chemical Neuroscience
IS - 7
ER -
