Maccarrone Mauro, Battista Natalia, Centonze Diego
Department of Biomedical Sciences, University of Teramo, Piazza A. Moro 45, 64100 Teramo, Italy.
Prog Neurobiol. 2007 Apr;81(5-6):349-79. doi: 10.1016/j.pneurobio.2006.11.006. Epub 2007 Feb 2.
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.
内源性大麻素是大麻素受体的内源性激动剂，由长链多不饱和脂肪酸的酰胺、酯和醚组成。花生四烯酸乙醇胺（N-花生四烯酰乙醇胺）和2-花生四烯酸甘油酯是这类脂质介质中研究得最为深入的成员，目前人们普遍认为它们在体内的浓度和生物活性在很大程度上依赖于一种“代谢调控”。因此，合成、转运和降解内源性大麻素的蛋白质，以及与靶受体共同构成所谓“内源性大麻素系统”的蛋白质，成为了深入研究的焦点。本综述将介绍这一新系统，以便更好地透视其调节对亨廷顿舞蹈病的影响。特别是，将在亨廷顿舞蹈病的发病和进展背景下讨论内源性大麻素受体激动剂/拮抗剂或内源性大麻素代谢抑制剂的作用，并与帕金森病、阿尔茨海默病和肌萎缩侧索硬化症等其他神经退行性疾病进行比较。此外，还将综述内源性大麻素在多发性硬化症中的可塑性变化，以此作为其在神经炎症性疾病中作用的范例。
