Role of α‑synuclein in cognitive dysfunction: Studies in Drosophila melanogaster

Abstract α-Synuclein (α-Syn) is hypothesized to have a critical role in sporadic and genetic cases of Parkinson's disease (PD) in which Lewy bodies, as the hallmark of PD, are formed from abnormal aggregates of α-Syn. To determine the role of α-Syn in the motor and cognitive dysfunction observed in PD, a Drosophila melanogaster model was established to investigate the electrophysiological and ethological changes caused by overexpression of α-Syn. The present data indicated that α-Syn overexpression reduced the synaptic transmission of cholinergic neurons by modulating the calcium channel currents in the projection neurons in the antennal lobe region of the Drosophila brain, as well as the learning and memory ability of the flies. However, the locomotor ability of the Drosophila remained unaffected. The present findings suggested that α-Syn may be associated with senile dementia in patients with PD.