| Summary: | 碩士 === 國立臺灣師範大學 === 生命科學研究所 === 99 === Spinocerebellar ataxia type 3 (SCA3), also called Machado–Joseph disease (MJD), is an autosomal dominant neurodegenerative disease results from expanded CAG repeat of MJD1 gene. The CAG repeat expansion encodes polyglutamine (polyQ) stretch in mutant ataxin-3 protein and causes protein cleaved, insoluble, accumulated and aggregated in the neurons. These inclusions further elevate cellular oxidative stress and lead to cell death. We established inducible cell system expressing human full length ataxin-3 containing 27Q or 75Q in PC12 cells. Cells with 75Q ataxin-3 showed lower viability and more nuclear/peri-nuclear aggregation in stress environments. We tested several novel HDAC inhibitor (HDACi) compounds in the inducible SCA3 cells. Our results show that some HDACi could elevate cell viability, reduce aggregation and promote neurite outgrowth. We also observed that HDACi could increase histone acetylation and activate neuroprotective proteins, such as Hsp27, ERK pathway regulators, MnSOD and NF-κB. These findings indicate that some novel HDACi compounds might be potential for SCA3 treatment.
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