2013年
Molecular pathogenesis of ALS in TDP43 era
Clinical Neurology
- 巻
- 53
- 号
- 11
- 開始ページ
- 1077
- 終了ページ
- 1079
- 記述言語
- 日本語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.5692/clinicalneurol.53.1077
To clarify the molecular pathogenesis of amyotrophic lateral sclerosis (ALS) associated with TAR-DNA binding protein 43?kDd (TDP-43), the quality and quantity of TDP-43 take a crucial role. Regarding to the quality of TDP-43, TDP-43 has been reported as an aggregate-prone protein. Especially the C-terminus of the TDP-43 tends to form aggregate and has prion-like domain. Interestingly the mutations in the genes, which produce proteins with prion-like domain, have been identified in several neurodegenerative disorders. These results suggest the existence of the common property in the causative proteins for neurodegenerative disorders. For the quantity of TDP-43, the adequate amount of TDP-43 is necessary for maintaining cell function and cell survival. The amount of TDP-43 is tightly regulated by TDP-43. However the mechanism for autoregulation has not been fully elucidated. For the function of TDP-43, TDP-43 locates at stress granule, GEM and associates with the large genes and introns. Thus the alteration of TDP-43 may affect the function of stress granule, GEM and RNA metabolism in several genes. Moreover a U12 type spliceosome, which is matured in GEM, is decreased in ALS. The investigation of whether these dysfunctions explain the selective pathology in ALS provides a new therapeutic strategy for ALS.
- リンク情報
- ID情報
-
- DOI : 10.5692/clinicalneurol.53.1077
- ISSN : 0009-918X
- PubMed ID : 24291884
- SCOPUS ID : 84891762421