The majority of neurodegenerative diseases are associated with excessive glutamatergic transmission, oxidative stress and/or inflammatory changes that lead to activation of the apoptotic cascade and subsequent neuronal demise. Cannabinoids have been demonstrated to confer neuroprotection both in vitro and in a number of in vivo paradigms of neurodegeneration including cerebral ischemia, hypoxia, seizures and experimental autoimmune encephalitis. The molecular mechanisms underlying cannabinoid-mediated protection involve both CB1 receptor-dependent and receptor-independent events. Anti-oxidant activities and the proclivity to reduce excessive glutamatergic synaptic activity underlie some of the neuroprotective effects of cannabinoids. The attenuation of pro-inflammatory signalling coupled with an induction of pro-survival growth factors and enhanced mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) activities have also been implicated in the ability of exogenous and endogenous cannabinoids to provide neuroprotection.
KeywordsPC12 Cell Experimental Allergic Encephalomyelitis Fatty Acid Amide Hydrolase Extracellular Regulate Kinase Extracellular Regulate Kinase Activation
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