The Endocannabinoid System and Alzheimer’s Disease
- 528 Downloads
The importance of the role of the endocannabinoid system (ECS) in neurodegenerative diseases has grown during the past few years. Mostly because of the high density and wide distribution of cannabinoid receptors of the CB1 type in the central nervous system (CNS), much research focused on the function(s) that these receptors might play in pathophysiological conditions. Our current understanding, however, points to much diverse roles for this system. In particular, other elements of the ECS, such as the fatty acid amide hydrolase (FAAH) or the CB2 cannabinoid receptor are now considered as promising pharmacological targets for some diseases and new cannabinoids have been incorporated as therapeutic tools. Although still preliminary, recent reports suggest that the modulation of the ECS may constitute a novel approach for the treatment of Alzheimer’s disease (AD). Data obtained in vitro, as well as in animal models for this disease and in human samples seem to corroborate the notion that the activation of the ECS, through the use of agonists or by enhancing the endogenous cannabinoid tone, may induce beneficial effects on the evolution of this disease.
KeywordsEndocannabinoid system Alzheimer’s disease Animal models
The authors’ work is supported by the Spanish Ministry of Education and Science (MEC-SAF 2004/00237) and by Mapfre Foundation.
- 9.Akiyama H, Barger S, Barnum S, Bradt B, Bauer J, Cole GM, Cooper NR, Eikelenboom P, Emmerling M, Fiebich BL, Finch CE, Frautschy S, Griffin WS, Hampel H, Hull M, Landreth G, Lue L, Mrak R, Mackenzie IR, McGeer PL, O’Banion MK, Pachter J, Pasinetti G, Plata-Salaman C, Rogers J, Rydel R, Shen Y, Streit W, Strohmeyer R, Tooyoma I, van Muiswinkel FL, Veerhuis R, Walker D, Webster S, Wegrzyniak B, Wenk G, Wyss-Coray T (2000) Inflammation and Alzheimer’s disease. Neurobiol Aging 21:383–421PubMedCrossRefGoogle Scholar
- 19.Esposito G, De Filippis D, Steardo L, Scuderi C, Savani C, Cuomo V, Iuvone T (2006) CB1 receptor selective activation inhibits beta-amyloid-induced iNOS protein expression in C6 cells and subsequently blunts tau protein hyperphosphorylation in co-cultured neurons. Neurosci Lett 404:342–346PubMedCrossRefGoogle Scholar
- 20.Van der Stelt M, Mazzola C, Esposito G, Matias I, Petrosino S, De Filippis D, Micale V, Drago F, Iuvone T, Di Marzo V (2006) Endocannabinoids and beta-amyloid-induced neurotoxicity in vivo: effect of pharmacological elevation of endocannabinoid levels. Cell Mol Life Sci 63:1410–1424PubMedCrossRefGoogle Scholar
- 21.Esposito G, De Filippis D, Maiuri MC, De Stefano D, Carnuccio R, Iuvone T (2006) Cannabidiol inhibits inducible nitric oxide synthase protein expression and nitric oxide production in beta-amyloid stimulated PC12 neurons through p38 MAP kinase and NF-kappaB involvement. Neurosci Lett 399:91–95PubMedCrossRefGoogle Scholar
- 33.Devine ML, Dow GJ, Greenberg BR, Holstein DW, Icaza L, Jue PY, Meyers FH, O’Brien E, Roberts CM, Rocchio GL (1987) Adverse reactions to delta-9-tetrahydrocannabinol given as an antiemetic in a multicenter study. Clin Pharmacol 6:319–322Google Scholar
- 34.Strasser F, Luftner D, Possinger K, Ernst G, Ruhstaller T, Meissner W, Ko YD, Schnelle M, Reif M, Cerny T (2006) Comparison of orally administered cannabis extract and delta-9-tetrahydrocannabinol in treating patients with cancer-related anorexia-cachexia syndrome: a multicenter, phase III, randomized, double-blind, placebo-controlled clinical trial from the Cannabis-In-Cachexia-Study-Group. J Clin Oncol 20;24:3394–3400CrossRefGoogle Scholar
- 38.Westlake TM, Howlett AC, Bonner TI, Matsuda LA, Herkenham M (1994) Cannabinoid receptor binding and messenger RNA expression in human brain: an in vitro receptor autoradiography and in situ hybridization histochemistry study of normal aged and Alzheimer’s brains. Neuroscience 63:637–652PubMedCrossRefGoogle Scholar