Pink1 RNAi and Parkin Expression in Drosophila melanogaster
Date
2011-06-03
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Abstract
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.
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Keywords
sporadic inclusion body myositis, Pink1, Parkin, amyloid, Parkinson's disease, Alzheimer's disease, mitochondria, Drosophila, hAPP, muscle