The endocannabinoid system in Parkinson's disease.
Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder of largely unknown etiology caused by a pathological cascade resulting in the degeneration of midbrain dopaminergic neurons of the substantia nigra pars compacta (SNpc) projecting to the nucleus striatum, the main input station of the basal ganglia neuronal circuit. The components of the endocannabinoid (ECB) system are highly expressed at different levels in the basal ganglia neural circuit where they bidirectionally interact with dopaminergic, glutamatergic and GABAergic signaling systems. In particular, at synapses linking cortical and striatal neurons, endocannabinoids (ECBs) are known to critically modulate synaptic transmission and to mediate the induction of a particular form of synaptic plasticity, the long-term depression. The evidence that ECBs play a central role in regulating basal ganglia physiology and motor function and the profound modifications occurring in ECB signaling after dopamine depletion in both experimental models of PD and patients suffering from the disease, provide support for the development of pharmacological compounds targeting the ECB system as symptomatic and neuroprotective therapeutic strategies for PD.
Di Filippo
Massimiliano
M
Clinica Neurologica, Ospedale S. Maria della Misericordia, Universita' di Perugia, 06156 Perugia, Italy.
Picconi
Barbara
B
Tozzi
Alessandro
A
Ghiglieri
Veronica
V
Rossi
Aroldo
A
Calabresi
Paolo
P
D000818:Animals; D001479:Basal Ganglia / Q000378:metabolism; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D004195:Disease Models, Animal; D004298:Dopamine / Q000172:deficiency / Q000378:metabolism; D016503:Drug Delivery Systems; D063388:Endocannabinoids; D006801:Humans; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism; D010300:Parkinson Disease / Q000188:drug therapy / Q000503:physiopathology*; D009435:Synaptic Transmission
D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D004298:Dopamine