标题:Activation of Mitochondrial Unfolded Protein Response in SHSY5Y Expressing APP Cells and APP/PS1 Mice
作者:Shen Y.; Ding M.; Xie Z.; Liu X.; Yang H.; Jin S.; Xu S.; Zhu Z.;等 更多
作者机构:[Shen, Y] Medicine School, Shandong University, Jinan, China;[ Ding, M] Medicine School, Shandong University, Jinan, China;[ Xie, Z] Department of Neu 更多
通讯作者:Wang, P(wping0108@163.com)
通讯作者地址:[Wang, P] Department of Neurology Medicine, Second Hospital of Shandong UniversityChina;
来源:Frontiers in Cellular Neuroscience
出版年:2020
卷:13
DOI:10.3389/fncel.2019.00568
关键词:Alzheimer disease; mevalonate pathway; simvastatin; sphingolipid biosynthesis pathway; UPRmt
摘要:Alzheimer disease (AD) is the most common form of dementia. Amyloid β-peptide (Aβ) deposition is a major neuropathologic feature of AD. When unfolded or misfolded proteins accumulate in mitochondria, the unfolded protein responses (UPRmt) is initiated. Numerous lines of evidence show that AD pathogenesis involves mitochondrial dysfunction. However little is known about whether the UPRmt is engaged in the process of AD development. In this study, we investigated the UPRmt in mouse and cell models of AD. We found that UPRmt was activated in the brain of 3 and 9 months old APP/PS1 mice, and in the SHSY5Y cells after exposure to Aβ25–35, Aβ25–35 triggered UPRmt in SHSY5Y cells could be attenuated upon administration of simvastatin or siRNA for HMGCS-1 to inhibit the mevalonate pathway, and or upon knocking down Serine palmitoyltransferase long chain subunit 1 (SPTLC-1) to lower sphingolipid biosynthesis. We observed that inhibition of UPRmt aggravated cytotoxic effects of Aβ25–35 in SHSY5Y cells. Our research suggests that the UPRmt activation and two pathways necessary for this response, and further provides evidence for the cytoprotective effect of UPRmt during the AD process. © Copyright © 2020 Shen, Ding, Xie, Liu, Yang, Jin, Xu, Zhu, Wang, Wang, Xu, Zhou, Wang and Bi.
收录类别:SCOPUS
资源类型:期刊论文
原文链接:https://www.scopus.com/inward/record.uri?eid=2-s2.0-85078221741&doi=10.3389%2ffncel.2019.00568&partnerID=40&md5=3ce14f80358055e1763c59f7c8b217fa
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