The synaptic function of parkin.
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.
San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy.
Jenny
J
Sassone
CNR Institute of Neuroscience, Department BIOMETRA, Università degli Studi di Milano, Milan, Italy.|IRCCS Istituto Auxologico Italiano, Department of Neurology and Laboratory of Neuroscience, Milan, Italy.
GiuliaMaia
G
Serratto
San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy.
Flavia
F
Valtorta
IRCCS Istituto Auxologico Italiano, Department of Neurology and Laboratory of Neuroscience, Milan, Italy.|Department of Pathophysiology and Transplantation, 'Dino Ferrari' Centre, Università degli Studi di Milano, Milan, Italy.
Vincenzo
V
Silani
CNR Institute of Neuroscience, Department BIOMETRA, Università degli Studi di Milano, Milan, Italy.
Maria
M
Passafaro
IRCCS Istituto Auxologico Italiano, Department of Neurology and Laboratory of Neuroscience, Milan, Italy.
Andrea
A
Ciammola
D000818:Animals; D059290:Dopaminergic Neurons / Q000502:physiology*; D006801:Humans; D009154:Mutation; D009410:Nerve Degeneration / Q000235:genetics; D010300:Parkinson Disease / Q000235:genetics / Q000503:physiopathology*; D009435:Synaptic Transmission / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000502:physiology*
D044767:Ubiquitin-Protein Ligases; C111567:parkin protein
Parkinson’s disease; dopamine; glutamate; parkin; synapse