`Rejuvenation' protects neurons in mouse models of Parkinson's disease
Abstract
Why dopamine-containing neurons of the brain's substantia nigra pars compacta die in Parkinson's disease has been an enduring mystery. Our studies suggest that the unusual reliance of these neurons on L-type Cav1.3 Ca2+ channels to drive their maintained, rhythmic pacemaking renders them vulnerable to stressors thought to contribute to disease progression. The reliance on these channels increases with age, as juvenile dopamine-containing neurons in the substantia nigra pars compacta use pacemaking mechanisms common to neurons not affected in Parkinson's disease. These mechanisms remain latent in adulthood, and blocking Cav1.3 Ca2+ channels in adult neurons induces a reversion to the juvenile form of pacemaking. Such blocking (`rejuvenation') protects these neurons in both in vitro and in vivo models of Parkinson's disease, pointing to a new strategy that could slow or stop the progression of the disease.
- Publication:
-
Nature
- Pub Date:
- June 2007
- DOI:
- 10.1038/nature05865
- Bibcode:
- 2007Natur.447.1081C