Cannabinoids and Neuroprotection in Motor-Related Disorders

Eva   de   Lago; Javier      Fernandez-Ruiz

Abstract

Neuroprotective properties of cannabinoids have been extensively studied in the last years in different neurodegenerative pathologies. This potential is based on the antioxidant, anti-inflammatory and anti-excitotoxic properties exhibited by these compounds that allow them to afford neuroprotection in different neurodegenerative disorders like Parkinsons disease (PD), Huntingtons disease (HD), multiple sclerosis (MS) and others. PD and HD are chronic pathologies that are caused by the degeneration of specific structures within the basal ganglia. In both disorders, the key mechanisms involved in the neuroprotection provided by cannabinoids include cannabinoid receptor-independent effects aimed at reducing the oxidative injury, and also cannabinoid 2 receptors (CB2)-mediated effects exerted by regulating the influence of reactive microglia on neuronal homeostasis. MS is an inflammatory demyelinating disorder primarily affecting spinal neurons and secondarily producing a malfunctioning and/or degeneration of other neuronal subpopulations located in supraspinal brain structures. There is evidence that both cannabinoid 1 receptors (CB1) and CB2 may afford a protective effect in this disease due to their immunomodulatory, anti-inflammatory and anti-excitotoxic properties. Lastly, neuroprotective effects of cannabinoids exerted by the activation of CB1 but also CB2 receptors have been also identified in amyotrophic lateral sclerosis (ALS), another degenerative disease characterized by the selective death of spinal motoneurons. In the present review, we will collect the latest advances in the knowledge of the cellular and molecular mechanisms through which cannabinoids might arrest/delay the degeneration of specific neuronal subpopulations in these motor-related disorders. This should serve to encourage that the present promising evidence obtained mainly at the preclinical level might progress to a real exploitation of neuroprotective benefits of potential cannabinoid-based medicines.

Keywords: Cannabinoids, cannabinoid signalling system, CB1 receptors, CB2 receptors, neurodegeneration, neuroprotection, Parkinson's disease, Huntington's disease, multiple sclerosis, amyotrophic lateral sclerosis