Symptoms of Parkinson Disease (PD), the second most common neurodegenerative disease, emerge
due to degeneration of dopaminergic neurons. Recently, a genome wide study revealed a role for a foxo transcription factor in PD. In the model organism Drosophila melanogaster, we have attempted
1) to inhibit the sole Drosophila homologue of foxo through the directed expression of a
stable inducible RNAi transgene and 2) to indirectly increase foxo transcription activity through
the inhibition of the kinase minibrain (mnb), a foxo transcriptional inhibitor. To evaluate the lifetime
consequences upon the flies, longevity assays and locomotion over time assays were conducted.
The inhibition of foxo by foxo-RNAi decreases life span significantly when expressed under
the control of Tyrosine Hydroxylase-Gal4 (TH-Gal4). The targeted expression of mnb-RNAi, in the
dopaminergic neurons, with an expected loss of suppression of foxo transcriptional activity, results
in a significant loss of climbing ability. Thus alteration of foxo activity, both by RNA-inhibition
and by down-regulation of an inhibitor of foxo, minibrain, produces novel Drosophila models of
Parkinson Disease.
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