title: Parkinson's disease: don't mess with calcium.
abstract: The hallmark of the movement disorder Parkinson's disease (PD) is progressive degeneration of dopaminergic neurons. Mitochondrial dysfunction, impaired ubiquitin-mediated proteolysis of α-synuclein, and ER stress are each implicated in the complex and poorly understood sequence of events leading to dopaminergic neuron demise. In this issue of the JCI, Selvaraj et al. report that in a mouse neurotoxin-based model of PD, reduced Ca2+ influx through transient receptor potential C1 (TRPC1) channels in the plasma membrane of dopaminergic neurons triggers a cell death-inducing ER stress response. These new findings suggest that TRPC1 channels normally function in Ca2+-mediated signaling pathways that couple adaptive/neurotrophic responses to metabolic and oxidative stress and suggest that disruption of these pathways may contribute to PD.
authors.affiliation: Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, Maryland 21224, USA. mattsonm@grc.nia.nih.gov
authors.forename: Mark P
authors.initials: MP
authors.lastname: Mattson
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D059290:Dopaminergic Neurons / Q000187:drug effects*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D006801:Humans; D008297:Male; D020734:Parkinsonian Disorders / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors*; D058570:TOR Serine-Threonine Kinases / Q000502:physiology*; D050052:TRPC Cation Channels / Q000096:biosynthesis*; D056811:Unfolded Protein Response / Q000187:drug effects*
chemical_list: D050052:TRPC Cation Channels; C096351:transient receptor potential cation channel, subfamily C, member 1; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; C546843:mTOR protein, mouse; C514862:Akt1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases