臨床神経学

第51回日本神経学会総会

<シンポジウム13―4>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
ポリグルタミン封入体結合タンパク質としてのFUS/TLS

貫名 信行

理化学研究所脳科学総合研究センター構造神経病理研究チーム〔〒351―0198 埼玉県和光市広沢2―1〕

Formation of intracellular aggregates is the hallmark of polyglutamine (polyQ) diseases. We analyzed the components of purified nuclear polyQ aggregates by mass spectrometry. As a result, we found that the RNAbinding protein translocated in liposarcoma (TLS) was one of the major components of nuclear polyQ aggregateinteracting proteins in a Huntington disease cell model and was also associated with neuronal intranuclear inclusions of polyQ diseases. In vitro study revealed that TLS could directly bind to truncated N-terminal huntingtin (tNhtt) aggregates but could not bind to monomer, indicating that the tNhtt protein acquired the ability to sequester TLS after forming aggregates. Immunohistochemistry showed that TLS was associated with neuronal intranuclear inclusions of Huntington disease and other poly Q disease brains. After this report, FUS/TLS was reported as a responsible gene for ALS6. Because TLS has a variety of functional roles, the sequestration of TLS to polyQ aggregates may play a role in diverse pathological changes in the brains of patients with polyQ diseases and ALS6.
Full Text of this Article in Japanese PDF (203K)

(臨床神経, 50:945−947, 2010)
key words:ポリグルタミン,凝集体,FUS/TLS,ALS6

(受付日:2010年5月22日)