Research progress of anti-Alzheimer′s disease drugs targeting Aβ oligomers
10.11665/j.issn.1000-5048.20210402
- VernacularTitle:基于Aβ寡聚体的阿尔茨海默病治疗药物研究进展
- Author:
Xiaofang LI
1
;
Longfei REN
;
Dandan WANG
;
Yuyan LI
Author Information
1. 中国药科大学药物化学系
- Publication Type:Journal Article
- Keywords:
Alzheimer''s disease;
Aβ protein;
Aβ oligomer;
therapeutic drugs;
advances
- From:
Journal of China Pharmaceutical University
2021;52(4):398-409
- CountryChina
- Language:Chinese
-
Abstract:
Alzheimer''s disease (AD) is the most common cause of senile dementia, accounting for an estimated 60% to 80% of cases, but there are no approved drugs to slow or stop the progressive clinical decline in the past years.Amyloid cascade hypothesis is recognized as the major etiologic basis for AD, however, the failures of several amyloid plaque-targeted programs have led many to dismiss the amyloid beta (Aβ) hypothesis of AD. Several reports show that soluble oligomers of Aβ (AβOs), which appear in brains more than 10 years before the clinical syndrome, are more toxic than Aβ plaque, causing synaptic dysfunction and neuronal apoptosis. Some agents that can effectively inhibit Aβ oligomer formation or block their toxicity made significant efficacy in clinical 2 and 3 trials, with the potential to be approved for the treatment of AD. This article reviews the recent development of AD drugs targeting Aβ oligomers, analyzes their structural characteristics, mechanism of action, preclinical and clinical data, and discusses the future direction of AD treatment, thus providing new strategies for AD drug research.
