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[阿尔茨海默病基因组分析揭示的新兴治疗靶点]

[Emerging Therapeutic Targets Revealed by Genome Analysis in Alzheimer's Disease].

作者信息

Ikeuchi Takeshi

机构信息

Department of Molecular Genetics, Brain Research Institute, Niigata University.

出版信息

Brain Nerve. 2017 Jul;69(7):789-798. doi: 10.11477/mf.1416200822.

Abstract

Cutting-edge genomics technologies have substantially improved our understanding of the pathogenesis of Alzheimer's disease (AD). The identification of mutations in APP, PSEN1, and PSEN2 causative for autosomal dominant AD (ADAD) has provided the basis of the "amyloid cascade" hypothesis of the pathogenetic mechanism of AD. While a number of therapeutic candidates targeting amyloid-β were developed using genetically engineered mouse models of ADAD, none have proven successful in mitigating the symptoms of AD in phase III clinical trials. Thus, we must reconsider the modification of AD pathogenesis by targets within the amyloid cascade, and explore new targets for AD therapy. This review provides a comprehensive summary of the recent genetic studies of AD from this perspective, and discusses prospective and emerging therapeutic interventions for patients with AD.

摘要

前沿的基因组学技术极大地增进了我们对阿尔茨海默病(AD)发病机制的理解。APP、PSEN1和PSEN2基因的突变被鉴定为常染色体显性AD(ADAD)的致病因素,这为AD发病机制的“淀粉样蛋白级联反应”假说提供了基础。虽然利用ADAD基因工程小鼠模型开发了许多靶向淀粉样β蛋白的治疗候选药物,但在III期临床试验中,没有一种药物被证明能成功减轻AD症状。因此,我们必须重新考虑通过淀粉样蛋白级联反应中的靶点来改变AD的发病机制,并探索AD治疗的新靶点。本综述从这一角度全面总结了AD近期的遗传学研究,并讨论了AD患者的前瞻性和新兴治疗干预措施。

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