To elucidate the molecular mechanisms of "gain of toxic function" of expanded polyglutamine stretches in CAG repeat expansion diseases, the inventors established an expression system of full-length and truncated cDNAs for dentatorubral-pallidoluysian atrophy (DRPLA) and found that truncated DRPLA proteins containing the expanded polyglutamine stretch, but not the full-length protein, form peri- and intra-nuclear aggregates consisting of filaments and concomitant apoptosis. The apoptotic cell death was partially suppressed by transglutaminase inhibitors, cystamine and monodansyl cadaverine, raising the possibility of involvement of transglutaminase reaction. The results may provide a potential basis for the development of therapeutic measures for CAG repeat expansion diseases.

Niigata University

Remedy for CAG repeat expansion diseases

Diseases Mediated by transglutaminase, such as Huntington's Disease, spinobulbar atrophy, spinocerebellar ataxia, and dentatorubralpallidoluysian atrophy, as well as inflammatory diseases of the central nervous system, including mautiple sclerosis, rheumatoid arthritis, and insulin dependent diabetes mellitus, can be treated by administering a transglutaminase inhibitor such as monadansyl cadaverine, monoamines and diamines such as cystamine, putrescine, GABA. (gamma-amino benzoic acid), N-benzyloxy carbonyl, 5-deazp-4-oxonorvaline p-nitrophenylester, glycine methyl ester, CuSO4, and the oral anti-hyperglycemic agent tolbutamide.

cadaverine/ניוון ביולוגיה

Remedy for CAG repeat expansion diseases

Method and compositions for treating diseases mediated by transglutaminase activity

המאגר השלם ביותר של צמחי מרפא המגובה על ידי המדע