The endocannabinoid pathway in Huntington's disease: a comparison with other neurodegenerative diseases

Endocannabinoids are endogenous agonists of cannabinoid receptors, and comprise amides, esters and ethers of long chain polyunsaturated fatty acids. Anandamide (N-arachidonoylethanolamine) and 2-arachidonoylglycerol are the best-studied members of this class of lipid mediators, and it is now widely accepted that their in vivo concentration and biological activity are largely dependent on a “metabolic control.” Therefore, the proteins that synthesize, transport and degrade endocannabinoids, and that together with the target receptors form the so-called “endocannabinoid system,” are the focus of intense research. This new system will be presented in this review, in order to put in a better perspective the impact of its modulation on Huntington's disease. In particular, the effect of agonists/antagonists of endocannabinoid receptors, or of inhibitors of endocannabinoid metabolism, will be discussed in the context of onset and progression of Huntington's disease, and will be compared with other neurodegenerative diseases like Parkinson's disease, Alzheimer's disease, and amyotropic lateral sclerosis. Also the plastic changes of endocannabinoids in multiple sclerosis will be reviewed, as a paradigm of their impact in neuroinflammatory disorders.