期刊
JOURNAL OF MOLECULAR NEUROSCIENCE
卷 29, 期 2, 页码 153-168出版社
HUMANA PRESS INC
DOI: 10.1385/JMN:29:2:153
关键词
inclusion bodies; chaperone; tau; cytoskeleton; proteasome; mitochondria
Ubiquitinated tau-positive inclusion bodies in oligodendrocytes are consistent features in a variety of neurodegenerative disorders, and their formation points to an underlying incapacity of the protein quality control system that normally prevents the accumulation of misfolded proteins. To study the consequences of proteasomal impairment, we have used an oligodendroglial cell fine, namely OLN-t40 cells, genetically engineered to express the longest human tau isoform. Treatment of OLN-t40 cells with the proteasomal inhibitor MG-132 (0.5 mu M, 18 h) caused the formation of large, nonfibrillary tau-positive aggregates containing the small HSP alpha B-crystallin and ubiquitin in the vicinity of the microtubule organizing center (MTOC). The sequestration of misfolded proteins into specialized regions, called aggresomes, in response to stress stimuli has been reported to be associated with a redistribution of intermediate filaments (IFs). In oligodendroglial cells, which do not contain a cytoplasmic IF system, aggresome-like inclusions were instead surrounded by bundles of MTs and contained clusters of mitochondria. Aggresome formation was prevented by both MT-stabilizing and -destabilizing drugs, indicating not only that an intact cytoskeleton but also the dynamic instability of the MT network is required. Furthermore, the binding of stress-induced alpha B-crystallin to the MTs points to a possible protective role during disease progression.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据