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 Ca(2+) 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 Ca(2+) homeostasis in DA neurodegeneration and protection. Our data showed that the Ca(2+) chelator EGTA is neuroprotective against a PD toxin MPP(+) (40μM). We also use the genetic tools available in Drosophila to manipulate Ca(2+) channel activity. DA neurons lacking functional Ca(2+) channels (i.e., cacophony mutant) are inherently protected against MPP(+) toxicity. Furthermore, overexpression of wild type Ca(2+) channels in DA neurons blocks the rescue effect of a D2 agonist quinpirole on DA neurodegeneration. Our findings support the idea that Ca(2+) is a source of vulnerability for DA neurons and that the modulation of Ca(2+) levels in DA neurons could be a potential neuroprotective treatment.
