Journal
AGING AND DISEASE
Volume -, Issue -, Pages -Publisher
INT SOC AGING & DISEASE
DOI: 10.14336/AD.2022.0412
Keywords
Alzheimer's disease; amyloid cascade hypothesis; drug development strategy; clinical trials
Categories
Funding
- Scientific Research Project of Education Department of Zhejiang Province [Y202147325]
- National Training Program of Innovation and Entrepreneurship for Undergraduates [202110341055, 20210 1341012]
- Zhejiang Provincial Key Laboratory of Resources Protection and Innovation of Traditional Chinese Medicine [2021E10013]
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The amyloid cascade hypothesis has been a key focus in Alzheimer's disease therapeutic research. This review discusses the current hypothesis and pathogenesis, as well as drug development strategies targeting different stages in this hypothesis. Strategies like immunotherapy have shown promising results in clinical trials, but success rates remain low. The review also highlights common problems in drug development and emphasizes the importance of multidisciplinary cooperation and a better understanding of the amyloid cascade hypothesis.
The amyloid cascade hypothesis has always been a research focus in the therapeutic field of Alzheimer's disease (AD) since it was put forward. Numerous researchers attempted to find drugs for AD treatment based on this hypothesis. To promote the research of anti-AD drugs development, the current hypothesis and pathogenesis were reviewed with expounding of beta-amyloid generation from its precursor protein and related transformations. Meanwhile, the present drug development strategies aimed at each stage in this hypothesis were also summarized. Several strategies especially immunotherapy showed the optimistic results in clinical trials, but only a small percentage of them eventually succeeded. In this review, we also tried to point out some common problems of drug development in preclinical and clinical studies which might be settled through multidisciplinary cooperation as well as the understanding that reinforces the amyloid cascade hypothesis.
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