Investigate the effects of miR196a on mitochondrial functions in Huntington’s disease

  • 林 佳葳

Student thesis: Master's Thesis


Huntington’s disease (HD) is a dominant heritable and neurodegenerative disease It is caused by an expansion of CAG repeats in exon1 of the Huntingtin (HTT) gene Mutant HTT has been reported to impair mitochondrial functions causing decrease of mitochondrial membrane potential and ATP production and increase of oxidative stress In our previous studies miR-196a provides beneficial effects in HD However the protective mechanism of miR-196a on mitochondrial functions is still unknown We hypothesize miR-196a might promote mitochondrial functions in HD In this study we examined the effects of miR-196a on mitochondrial functions in HD striatal cells and HD transgenic mice The results showed the mitochondrial dysfunction in HD striatal cells and HD transgenic mice Furthermore we also found miR-196a could reduce oxidative stress in HD striatal cells One of antioxidant genes is nuclear factor erythroid 2 related factor 2 (Nrf2) which is related to antioxidant pathway and it is associated with mitochondrial functions The results indicated the expression level of Nrf2 is decreased in HD striatal cells Moreover miR-196a could activate translocation of Nrf2 into nucleus We also found miR-196a could increase the expression level of the downstream gene HO-1 In sum our results suggested mitochondrial dysfunction was found in HD and miR-196a might improve mitochondrial functions through Nrf2 pathway We anticipate miR-196a should be important for mitochondrial functions and improved mitochondrial functions may contribute to therapeutic strategies for HD
Date of Award2018 Aug 10
Original languageEnglish
SupervisorShang-Hsun Yang (Supervisor)

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