Chronic treatment with 17-DMAG improves balance and coordination in a new mouse model of Machado-Joseph disease.
作者： Anabela Silva-Fernandes , Sara Duarte-Silva , Andreia Neves-Carvalho , Marina Amorim , Carina Soares-Cunha
DOI: 10.1007/S13311-013-0255-9
关键词:
摘要: Machado-Joseph disease (MJD) or spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative currently with no treatment. We describe novel mouse model of MJD which expresses mutant human ataxin-3 at near endogenous levels and manifests MJD-like motor symptoms that appear gradually progress over time. CMVMJD135 mice show intranuclear inclusions in the CNS changes key regions, such as pontine dentate nuclei. Hsp90 inhibition has shown promising outcomes some diseases, but nothing known about its effects MJD. Chronic treatment CMVMJD inhibitor 17-DMAG resulted delay progression their coordination deficits and, 22 24 weeks age, was able to rescue uncoordination phenotype wild-type levels; parallel, reduction neuropathology observed treated animals. limited induction heat-shock proteins treatment, found evidence may be acting through autophagy, LC3-II (both mRNA protein levels) beclin-1 were induced brain This decreased reduced aggregation this protein. Our data validate relevant tool for study pathogenesis pre-clinical studies, therapeutic strategy
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