title: The role of calcium and mitochondrial oxidant stress in the loss of substantia nigra pars compacta dopaminergic neurons in Parkinson's disease.
abstract: Parkinson's disease (PD) is the second most common neurodegenerative disease in developed countries. The core motor symptoms are attributable to the degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc). Why these neurons succumb in PD is not clear. One potential clue has come from the observation that the engagement of L-type Ca²⁺ channels during autonomous pacemaking elevates the sensitivity of SNc DA neurons to mitochondrial toxins used to create animal models of PD, suggesting that Ca²⁺ entry is a factor in their selective vulnerability. Recent work has shown that this Ca²⁺ entry also elevates mitochondrial oxidant stress and that this stress is exacerbated by deletion of DJ-1, a gene associated with an early onset, recessive form of PD. Epidemiological data also support a linkage between L-type Ca²⁺ channels and the risk of developing PD. This review examines the hypothesis that the primary factor driving neurodegenerative changes in PD is the metabolic stress created by Ca²⁺ entry, particularly in the face of genetic or environmental factors that compromise oxidative defenses or proteostatic competence.
authors: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. j-surmeier@northwestern.edu
authors: D J
authors: DJ
authors: Surmeier
authors: J N
authors: JN
authors: Guzman
authors: J
authors: J
authors: Sanchez-Padilla
authors: P T
authors: PT
authors: Schumacker
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology / Q000627:therapeutic use; D059290:Dopaminergic Neurons / Q000473:pathology* / Q000648:ultrastructure; D006801:Humans; D007980:Levodopa / Q000494:pharmacology / Q000627:therapeutic use; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010300:Parkinson Disease / Q000188:drug therapy / Q000473:pathology*; D013378:Substantia Nigra / Q000473:pathology*
chemical_list: D020746:Calcium Channels, L-Type; D015259:Dopamine Agents; D007980:Levodopa; D002118:Calcium