The Role of the Endocannabinoid System in Alzheimer's Disease: Facts and Hypotheses

摘要

Unlike other neuroinflammatory disorders, like Parkinson’s disease, Huntington’s disease and multiple sclerosis,little is still known of the role of the endocannabinoid system in Alzheimer’s disease (AD). This is partly due to thepoor availability of animal models that are really relevant to the human disease, and to the complexity of AD as comparedto other neurological states. Nevertheless, the available data indicate that endocannabinoids are likely to play in this disordera role similar to that suggested in other neurodegenerative diseases, that is, to represent an endogenous adaptive responseaimed at counteracting both the neurochemical and inflammatory consequences of -amyloid-induced tau proteinhyperactivity, possibly the most important underlying cause of AD. Furthermore, plant and synthetic cannabinoids, andparticularly the non-psychotropic cannabidiol, might also exert other, non-cannabinoid receptor-mediated protective effects,including, but not limited to, anti-oxidant actions. There is evidence, from in vivo studies on -amyloid-inducedneurotoxicity, also for a possible causative role of endocannabinoids in the impairment in memory retention, which istypical of AD. This might open the way to the use of cannabinoid receptor antagonists as therapeutic drugs for the treatmentof cognitive deficits in the more advanced phases of this disorder. The scant, but nevertheless important literature onthe regulation and role of the endocannabinoid system in AD, and on the potential treatment of this disorder with cannabinoidsand endocannabinoid-based drugs, are discussed in this mini-review.