Pink1 RNAi and Parkin Expression in Drosophila melanogaster
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Sporadic Inclusion Body Myositis (s-IBM) is a degenerative muscle disorder. Symptoms include muscle weakness and loss of motor control. Abnormal accumulation of human Amyloid Precursor Protein (hAPP) and its proteolytic fragments (Aß) are found in the protein aggregates characteristic of s- IBM pathology. The aggregates impair the function of the Ubiquitin Proteasome System (UPS), a cellular mechanism that degrades unwanted protein. Over- expression of Parkin, which encodes a UPS subunit, combats the detrimental effects of Aß accumulation. Parkin over-expression also ameliorates mitochondrial defects of knocked-out Pink1. Transgenic Drosophila melanogaster were used to investigate interactions between Pink1, Parkin and hAPP. The first part of this project found that expression of human Parkin reverses the negative behavioral effects of expressing, from a transgene, hAPP in fly musculature. The second part of this study used Pink1 RNAi flies to determine the effect Pink1 RNA interference has on endogenous Parkin expression in skeletal musculature. qPCR techniques revealed no differential expression of endogenous Parkin between wild-type and Pink1 RNAi flies of various ages. Complementarily, Transmission Electron Microscopy on indirect flight muscle revealed the absence of hypothesized mitochondrial abnormalities in all flies but one; however, other morphological differences were found. The focus of this project was to ascertain potential therapeutic effects of Parkin.