Glutathione depletion and overproduction both initiate degeneration of nigral dopaminergic neurons.

ABSTRACT: Parkinson's disease is a neurodegenerative disorder characterized by severe motor deficits mainly due to degeneration of dopaminergic neurons in the substantia nigra. Decreased levels of the cell's most important anti-oxidant, glutathione, have been detected in nigral neurons of Parkinson patients, but it is unknown if they are the cause or merely the consequence of the disease. To elucidate if glutathione depletion causes selective degeneration of nigral dopaminergic neurons, we down-regulated glutathione synthesis in different brain areas of adult rats by a viral vector-based RNAi approach. Decreased glutathione synthesis resulted in progressive degeneration of nigral dopaminergic neurons, while extra-nigral and striatal neurons were significantly less vulnerable. Degeneration of dopamin

SUBMITTER: Garrido M 

PROVIDER: S-EPMC3058355 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature