Description:
<jats:p>One of the hallmarks of Parkinson's Disease (PD) is aggregation of incorrectly folded α-synuclein (<jats:italic>SNCA</jats:italic>) protein resulting in selective death of dopaminergic neurons. Another form of PD is characterized by the loss-of-function of an E3-ubiquitin ligase, <jats:italic>parkin</jats:italic>. Mutations in <jats:italic>SNCA</jats:italic> and <jats:italic>parkin</jats:italic> result in impaired mitochondrial morphology, causing loss of dopaminergic neurons. Despite extensive research on the individual effects of <jats:italic>SNCA</jats:italic> and <jats:italic>parkin</jats:italic>, their interactions in dopaminergic neurons remain understudied. Here we employ <jats:italic>Drosophila</jats:italic> model to study the effect of collective overexpression of <jats:italic>SNCA</jats:italic> along with the downregulation of <jats:italic>parkin</jats:italic> in the dopaminergic neurons of the posterior brain. We found that overexpression of <jats:italic>SNCA</jats:italic> along with downregulation of <jats:italic>parkin</jats:italic> causes a reduction in the number of dopaminergic neuronal clusters in the posterior region of the adult brain, which is manifested as progressive locomotor dysfunction. Overexpression of <jats:italic>SNCA</jats:italic> and downregulation of <jats:italic>parkin</jats:italic> collectively results in altered mitochondrial morphology in a cluster-specific manner, only in a subset of dopaminergic neurons of the brain. Further, we found that <jats:italic>SNCA</jats:italic> overexpression causes transcriptional downregulation of <jats:italic>parkin</jats:italic>. However, this downregulation is not further enhanced upon collective <jats:italic>SNCA</jats:italic> overexpression and <jats:italic>parkin</jats:italic> downregulation. This suggests that the interactions of <jats:italic>SNCA</jats:italic> and <jats:italic>parkin</jats:italic> may not be additive. Our study thus provides insights into a potential link between α<jats:italic>-synuclein</jats:italic> and <jats:italic>parkin</jats:italic> interactions. These interactions result in altered mitochondrial morphology in a cluster-specific manner for dopaminergic neurons over a time, thus unraveling the molecular interactions involved in the etiology of Parkinson's Disease.</jats:p>