Role of Drosophila calcium channel cacophony in dopaminergic neurodegeneration and neuroprotection

Abstract

One of the most important questions in Parkinson’s disease (PD) regards the selective vulnerability of a specific population of dopaminergic (DA) neurons. Recent reports identify Ca2+ channel as a potential source of this vulnerability. This work uses a Drosophila primary neuronal cell culture system as an in vitro PD model to explore the role of Ca2+ homeostasis in DA neurodegeneration and protection. Our data showed that the Ca2+ chelator EGTA is neuroprotective against a PD toxin MPP+ (40μM). We also use the genetic tools available in Drosophila to manipulate Ca2+ channel activity. DA neurons lacking functional Ca2+ channels (i.e., cacophony mutant) are inherently protected against MPP+ toxicity. Furthermore, overexpression of wild type Ca2+ channels in DA neurons blocks the rescue effect of a D2 agonist quinpirole on DA neurodegeneration. Our findings support the idea that Ca2+ is a source of vulnerability for DA neurons and that the modulation of Ca2+ levels in DA neurons could be a potential neuroprotective treatment.