期刊
AMERICAN JOURNAL OF PATHOLOGY
卷 184, 期 3, 页码 790-799出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ajpath.2013.11.018
关键词
-
类别
资金
- JSPS [25430058, 25830045]
- Grants-in-Aid for Scientific Research [25830045, 25430058] Funding Source: KAKEN
Multiple system atrophy is an intractable neurodegenerative disease caused by alpha-synuclein (alpha-syn) accumulation in oLigodendrocytes and neurons. With the use of a transgenic mouse model overexpressing human alpha-syn in oligodendrocytes, we demonstrated that oligodendrocytic alpha-syn inclusions induce neuronal alpha-syn accumulation, resulting in progressive neuronal degeneration. The mechanism through which oligodendrocytic alpha-syn inclusions trigger neuronal alpha-syn accumulation leading to multiple system atrophy is unknown. In this study, we identified cystatin C, an oligodendrocyte-derived secretory protein that triggers alpha-syn up-regulation and insoluble alpha-syn accumulation, in neurons of the mouse central nervous system. Cystatin C was released by mouse oligodendrocytes overexpressing human alpha-syn, and extracellular cystatin C increased the expression of the endogenous alpha-syn gene in wild-type mouse neurons. These neurons then accumulate insoluble alpha-syn and may undergo apoptosis. Cystatin C is a potential pathogenic signal triggering neurodegeneration in multiple system atrophy.
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