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靶向雷帕霉素靶蛋白以减少阿尔茨海默病相关的认知衰退:从当前的研究进展到未来的治疗方法

Targeting mTOR to reduce Alzheimer-related cognitive decline: from current hits to future therapies.

作者信息

Tramutola Antonella, Lanzillotta Chiara, Di Domenico Fabio

机构信息

a Department of Biochemical Sciences , Sapienza University of Rome , Rome , Italy.

出版信息

Expert Rev Neurother. 2017 Jan;17(1):33-45. doi: 10.1080/14737175.2017.1244482. Epub 2016 Oct 14.

Abstract

The mTOR pathway is involved in the regulation of a wide repertoire of cellular functions in the brain and its dysregulation is emerging as a leitmotif in a large number of neurological disorders. In AD, altered mTOR signaling contributes to the inhibition of autophagy deposition of Aβ and tau aggregates and to the alteration of several neuronal metabolic pathways. Areas covered: In this review, we report all the current findings on the use of mTOR inhibitors (rapamycin, rapalogues) in the treatment of AD. These results support the role of mTOR inhibitors as potential therapeutic agents able to reduce AD hallmarks and recover cognitive performances. Expert commentary: Despite mTOR inhibitors appearing to be ideal compounds to counteract AD, further studies are needed in order to gain knowledge on the involvement of aberrant mTOR in AD, and to standardize a valuable therapeutic approach that can be translated to humans.

摘要

mTOR信号通路参与大脑中多种细胞功能的调节,其失调正成为众多神经疾病的一个共同主题。在阿尔茨海默病(AD)中,mTOR信号改变会导致自噬抑制、β淀粉样蛋白(Aβ)和tau蛋白聚集体沉积以及多种神经元代谢途径的改变。涵盖领域:在本综述中,我们报告了目前关于使用mTOR抑制剂(雷帕霉素、雷帕霉素类似物)治疗AD的所有研究结果。这些结果支持mTOR抑制剂作为潜在治疗药物的作用,能够减少AD的特征并恢复认知功能。专家评论:尽管mTOR抑制剂似乎是对抗AD的理想化合物,但仍需要进一步研究,以了解异常mTOR在AD中的作用,并规范一种有价值的、可转化应用于人类的治疗方法。

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