期刊
CELL REPORTS
卷 4, 期 1, 页码 124-134出版社
CELL PRESS
DOI: 10.1016/j.celrep.2013.06.007
关键词
-
类别
资金
- JSPS KAKENHI [22500345, 23228004, 23240050]
- MHLW Grant [12946221]
- MEXT KAKENHI [24111556]
- Takeda Science Foundation
- Grants-in-Aid for Scientific Research [24111556, 24500429, 23591694, 25110738, 23700433, 22500345, 23240050] Funding Source: KAKEN
TDP-43 is the major component protein of ubiquitin-positive inclusions in brains of patients with frontotemporal lobar degeneration (FTLD-TDP) or amyotrophic lateral sclerosis (ALS). Here, we report the characterization of prion-like properties of aggregated TDP-43 prepared from diseased brains. When insoluble TDP-43 from ALS or FTLD-TDP brains was introduced as seeds into SH-SY5Y cells expressing TDP-43, phosphorylated and ubiquitinated TDP-43 was aggregated in a self-templating manner. Immunoblot analyses revealed that the C-terminal fragments of insoluble TDP-43 characteristic of each disease type acted as seeds, inducing seed-dependent aggregation of TDP-43 in these cells. The seeding ability of insoluble TDP-43 was unaffected by proteinase treatment but was abrogated by formic acid. One subtype of TDP-43 aggregate was resistant to boiling treatment. The insoluble fraction from cells harboring TDP-43 aggregates could also trigger intracellular TDP-43 aggregation. These results indicate that insoluble TDP-43 has prion-like properties that may play a role in the progression of TDP-43 proteinopathy.
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