第51回日本神経学会総会
＜シンポジウム13―2＞筋萎縮性側索硬化症の病因TDP-43およびFUS/TLS研究の最前線
TDP-43/ALSの臨床と病理
小野寺 理1）, 横関 明男2）, 譚 春鳳3）, 石原 智彦1）2）, 西平 靖3）, 豊島 靖子3）, 柿田 明美3）, 西澤 正豊2）, 高橋 均3）
1）新潟大学脳研究所生命科学リソース研究センター〔〒951―8585 新潟市中央区旭町通1番町757〕
2）同 神経内科
3）同 病態神経科学部門
The molecular pathogenesis of amyotrophic lateral sclerosis (ALS) is unclear. TAR DNA-binding proteins of 43 KDa (TDP-43) immunopositive cytoplasmic inclusions have been found in glia and neurons of ALS patients. The discovery of TDP-43 mutations in ALS patients indicates a direct role of TDP-43 in ALS. More than 30 mutations in the TDP-43 gene have been identified in patients with familial and sporadic ALS. ALS with a TDP-43 mutation is classified as ALS-10. The clinical features of ALS-10 are quite similar to those of sporadic ALS. Furthermore, the neuropathological findings for ALS-10, including TDP-43 immunopositive inclusions and Bunina bodies, are identical to those in sporadic ALS. Most of the mutations are located in the C-terminus of TDP-43, which may function as a binding domain of heterogeneous nuclear ribonucleoprotein. Frontotemporal lobar degeneration: FTLD and FTLD MND (motor neuron disease) also have TDP-43 immunopositive inclusions. These disorders have been named as TDP-43 proteinopathy. However, patients with TDP-43 mutations rarely develop FTLD. Causative genes for familial FTLD and FTLD/MND are not linked to the TDP-43 gene. Thus, other factors may contribute to the TDP-43 pathology in these diseases. Further analysis is required to elucidate the molecular mechanism of ALS-10 and TDP-43 proteinopathy.
Full Text of this Article in Japanese PDF (180K)
(臨床神経, 50：940−942, 2010)
key words：TDP-43，家族性ALS10型，病理，孤発性ALS，運動ニューロン病をともなう前頭側頭葉変性症
（受付日：2010年5月22日）
