کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4338723 1614878 2011 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The role of calcium and mitochondrial oxidant stress in the loss of substantia nigra pars compacta dopaminergic neurons in Parkinson's disease
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
The role of calcium and mitochondrial oxidant stress in the loss of substantia nigra pars compacta dopaminergic neurons in Parkinson's disease
چکیده انگلیسی

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.This article is part of a Special Issue entitled: Function and Dysfunction of the Basal Ganglia.

▶The motor symptoms of PD largely are attributable to the death of DA neurons in the SNc ▶The selective vulnerability of these neurons might be due to their engagement of low threshold l-type Ca2+ channels during pacemaking. This engagement elevates mitochondrial oxidant stress. ▶These channels are antagonized by dihydropyridines that are approved for human use and have been linked by epidemiological studies to reduced risk of PD.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 198, 15 December 2011, Pages 221–231
نویسندگان
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