期刊
FEBS JOURNAL
卷 278, 期 19, 页码 3539-3549出版社
WILEY
DOI: 10.1111/j.1742-4658.2011.08256.x
关键词
amyotrophic lateral sclerosis; frontotemporal dementia; motor neuron disease; prion domain; protein aggregation; RNA metabolism
资金
- NIH/NINDS [K08 NS055980, R01 NS069669]
- Muscular Dystrophy Association [135428]
- Children's Discovery Institute
- Burroughs Wellcome Fund
Accumulations of aggregated proteins are a key feature of the pathology of all of the major neurodegenerative diseases. Amyotrophic lateral sclerosis (ALS) was brought into this fold quite recently with the discovery of TDP-43 (TAR DNA binding protein, 43 kDa) inclusions in nearly all ALS cases. In part this discovery was fueled by the recognition of the clinical overlap between ALS and frontotemporal lobar degeneration, where ubiquitinated TDP-43 inclusions were first identified. Later the identification of TDP-43 mutations in rare familial forms of ALS confirmed that altered TDP-43 function can be a primary cause of the disease. However, the simple concept that TDP-43 is an aggregation-prone protein that forms toxic inclusions capable of promoting neurodegeneration has not been upheld by initial investigations. This review discusses observations from human pathology, cell culture and animal model systems, to highlight our somewhat murky understanding of the relationship between TDP-43 aggregation and neurodegeneration.
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