Abstract
Parkinsons 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.
Keywords: Parkinson's disease, endocannabinoids, synaptic plasticity, neuroinflammation
Current Pharmaceutical Design
Title: The Endocannabinoid System in Parkinsons Disease
Volume: 14 Issue: 23
Author(s): Massimiliano Di Filippo, Barbara Picconi, Alessandro Tozzi, Veronica Ghiglieri, Aroldo Rossi and Paolo Calabresi
Affiliation:
Keywords: Parkinson's disease, endocannabinoids, synaptic plasticity, neuroinflammation
Abstract: Parkinsons 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.
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Di Filippo Massimiliano, Picconi Barbara, Tozzi Alessandro, Ghiglieri Veronica, Rossi Aroldo and Calabresi Paolo, The Endocannabinoid System in Parkinsons Disease, Current Pharmaceutical Design 2008; 14 (23) . https://dx.doi.org/10.2174/138161208785740072
DOI https://dx.doi.org/10.2174/138161208785740072 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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