ASK1/p38 级联在阿尔茨海默病和大脑老化小鼠模型中的作用。

Role of ASK1/p38 Cascade in a Mouse Model of Alzheimer's Disease and Brain Aging.

机构信息

Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Chuo-ku, Kumamoto, Japan.

Laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.

出版信息

J Alzheimers Dis. 2018;61(1):259-263. doi: 10.3233/JAD-170645.

DOI:10.3233/JAD-170645

PMID:29154282

Abstract

To examine the role of ASK1 in Alzheimer's disease (AD), we generated 5XFAD mice deficient in ASK1 and investigated the characteristics of old 5XFAD and wild-type mice with ASK1 deficiency. ASK1 deficiency improved cognitive function in 24-month-old 5XFAD mice, which was associated with the reduction of phosphorylated p38. Thus, ASK1/p38 cascade seems to play some role in the pathogenesis of AD in mice. In 24-month-old wild-type mice, ASK1 deficiency increased cerebral vasoreactivity to acetazolamide and significantly reduced brain soluble Aβ, which were also associated with the reduction of phosphorylated p38. Thus, ASK1/p38 cascade may contribute to brain aging of wild-type mice. Collectively, our present results provided the evidence suggesting the involvement of ASK1/p38 cascade in AD and brain aging.

摘要

为了研究 ASK1 在阿尔茨海默病（AD）中的作用，我们生成了 ASK1 缺失的 5XFAD 小鼠，并研究了老年 5XFAD 小鼠和 ASK1 缺失的野生型小鼠的特征。ASK1 缺失改善了 24 月龄 5XFAD 小鼠的认知功能，这与磷酸化 p38 的减少有关。因此，ASK1/p38 级联似乎在小鼠 AD 的发病机制中起一定作用。在 24 月龄的野生型小鼠中，ASK1 缺失增加了对乙酰唑胺的脑血管反应性，并显著降低了脑可溶性 Aβ，这也与磷酸化 p38 的减少有关。因此，ASK1/p38 级联可能导致野生型小鼠的大脑衰老。总的来说，我们目前的结果提供了证据表明 ASK1/p38 级联参与 AD 和大脑衰老。