TITLE

The HtrA2 Drosophila model of Parkinson's disease is suppressed by the pro-survival Bcl-2 Buffy

AUTHOR(S)
M'Angale, P. Githure; Staveley, Brian E.; Hilliker, A.
PUB. DATE
January 2017
SOURCE
Genome;2017, Vol. 60 Issue 1, p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Mutations in High temperature requirement A2 (HtrA2), also designated PARK13, which lead to the loss of its protease activity, have been associated with Parkinson's disease (PD). HtrA2 is a mitochondrial protease that translocates to the cytosol upon the initiation of apoptosis where it participates in the abrogation of inhibitors of apoptosis (IAP) inhibition of caspases. Here, we demonstrate that the loss of the HtrA2 function in the dopaminergic neurons of Drosophila melanogaster results in PD-like phenotypes, and we attempt to restore the age-dependent loss in locomotor ability by co-expressing the sole pro-survival Bcl-2 homologue Buffy. The inhibition of HtrA2 in the dopaminergic neurons of Drosophila resulted in shortened lifespan and impaired climbing ability, and the overexpression of Buffy rescued the reduction in lifespan and the age-dependent loss of locomotor ability. In supportive experiments, the inhibition of HtrA2 in the Drosophila eye results in eye defects, marked by reduction in ommatidia number and increased disruption of the ommatidial array; phenotypes that are suppressed by the overexpression of Buffy.
ACCESSION #
120530447

 

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