356회 A Potential Role of Tissue Transglutaminase (tTG) in the aggregat…

356회

연사 :  전 완 주, 강원대학교 의과대학 약리학교실

제목: A Potential Role of Tissue Transglutaminase (tTG) in the aggregate formation of mutant huntingtin in Huntington‘s Disease (HD)

Abstract

 The cause of Huntington‘s disease (HD) is a pathological expansion of the polyglutamine domain within the N-terminal region of huntingtin. Neuronal aggregates composed of mutant huntingtin within certain neuronal populations are a characteristic hallmark of HD. Because tissue transglutaminase (tTG) cross-links proteins into aggregates and polypeptide-bound glutamines are primary determining factors for tTG-catalyzed reactions, it has been hypothesized that tTG may contribute to the formation of aggregates. Therefore, it is of fundamental importance to establish whether tTG plays a role in the formation of aggregates. The preliminary studies demonstrated that tTG expression and transglutaminase activity are elevated in specific brain areas affected in HD in a grade-dependent manner. These data clearly indicate that tTG is elevated in HD brain and may play a role in the disease process. The final study demonstrated that tTG did not coprecipitate with mutant truncated huntingtin. Furthermore, tTG was totally excluded from the aggregates, and significantly increasing tTG expression had no effect on the number of aggregates or their intracellular localization. These findings clearly demonstrate that tTG is not required for aggregate formation and does not facilitate the process of aggregate formation. It is clear that tTG levels and activity increase in HD brain. However, the exact role(s) of tTG in the etiology of HD remain unclear. At present it seems unlikely that tTG plays a role in the formation of aggregates in HD brain.