title: 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 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(+) (40 μM). 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.
authors.affiliation: Neuroscience Program, Department of Biological Sciences, 213 Life Science Building, Ohio University, Athens, OH 45701, USA. Electronic address: lyle.wiemerslage@neuro.uu.se.
authors.forename: Lyle
authors.initials: L
authors.lastname: Wiemerslage
authors.affiliation: Neuroscience Program, Department of Biological Sciences, 213 Life Science Building, Ohio University, Athens, OH 45701, USA. Electronic address: leed1@ohio.edu.
authors.forename: Daewoo
authors.initials: D
authors.lastname: Lee
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity; D000818:Animals; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D065096:Calcium Chelating Agents / Q000494:pharmacology; D059290:Dopaminergic Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D004330:Drosophila / Q000166:cytology* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004492:Edetic Acid / Q000494:pharmacology; D004625:Embryo, Nonmammalian / Q000166:cytology; D009154:Mutation; D009410:Nerve Degeneration / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D010300:Parkinson Disease / Q000473:pathology; D061251:Primary Cell Culture; D019257:Quinpirole / Q000494:pharmacology; D017448:Receptors, Dopamine D2 / Q000819:agonists
chemical_list: D015220:Calcium Channels; D065096:Calcium Chelating Agents; D029721:Drosophila Proteins; D018696:Neuroprotective Agents; D017448:Receptors, Dopamine D2; C472405:cac protein, Drosophila; D019257:Quinpirole; D004492:Edetic Acid; D015655:1-Methyl-4-phenylpyridinium
keywords: Cacophony; Calcium channel; Dopaminergic; Parkinson’s disease; Selective vulnerability