JOURNAL ARTICLE
REVIEW

The role of calcium and mitochondrial oxidant stress in the loss of substantia nigra pars compacta dopaminergic neurons in Parkinson's disease

D J Surmeier, J N Guzman, J Sanchez-Padilla, P T Schumacker
Neuroscience 2011 December 15, 198: 221-31
21884755
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.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
21884755
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"