Calcium, cellular aging, and selective neuronal vulnerability in Parkinson's disease.
Parkinson's disease (PD) is the second most common neurodegenerative disease in developed countries. The core motor symptoms are attributable to the degeneration of dopamine (DA) neurons in the substantia nigra pars compacta (SNc). Why these neurons, and other restricted sets of non-dopamine neuron, 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. Epidemiological data also supports 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 sustained Ca2+ entry, particularly in the face of genetic or environmental factors that compromise oxidative defenses or proteostatic competence.
Surmeier
D James
DJ
Department of Physiology, Feinberg School of Medicine, Northwestern University, 303 E. Chicago Ave., Chicago, IL 60611, USA. j-surmeier@northwestern.edu
Guzman
Jaime N
JN
Sanchez-Padilla
Javier
J
D000818:Animals; D001683:Biological Clocks; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism; D020013:Calcium Signaling; D016923:Cell Death; D016922:Cellular Senescence; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010300:Parkinson Disease / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D013312:Stress, Physiological; D013378:Substantia Nigra / Q000473:pathology
D020746:Calcium Channels, L-Type; D002118:Calcium; D004298:Dopamine