Journal
BRAIN
Volume 140, Issue -, Pages 2265-2272Publisher
OXFORD UNIV PRESS
DOI: 10.1093/brain/awx006
Keywords
parkin; Parkinson's disease; synapse; dopamine; glutamate
Categories
Funding
- Italian Ministry of Health [GR-2010-2318394]
- Cariplo Foundation [2012-0593]
- Telethon Foundation [GGP15167]
Ask authors/readers for more resources
Loss of function mutations in the gene PARK2, which encodes the protein parkin, cause autosomal recessive juvenile parkinsonism, a neurodegenerative disease characterized by degeneration of the dopaminergic neurons localized in the substantia nigra pars compacta. No therapy is effective in slowing disease progression mostly because the pathogenesis of the disease is yet to be understood. From accruing evidence suggesting that the protein parkin directly regulates synapses it can be hypothesized that PARK2 gene mutations lead to early synaptic damage that results in dopaminergic neuron loss over time. We review evidence that supports the role of parkin in modulating excitatory and dopaminergic synapse functions. We also discuss how these findings underpin the concept that autosomal recessive juvenile parkinsonism can be primarily a synaptopathy. Investigation into the molecular interactions between parkin and synaptic proteins may yield novel targets for pharmacologic interventions.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available