Biosynthesis of endocannabinoids and their modes of action in neurodegenerative diseases.
Endocannabinoids are thought to function as retrograde messengers, which modulate neurotransmitter release by activating presynaptic cannabinoid receptors. Anandamide and 2-arachidonoylglycerol (2-AG) are the two best studied endogenous lipids which can act as endocannabinoids. Together with the proteins responsible for their biosynthesis, inactivation and the cannabinoid receptors, these lipids constitute the endocannabinoid system. This system is proposed to be involved in various neurodegenerative diseases such as Parkinson's and Huntington's diseases as well as Multiple Sclerosis. It has been demonstrated that the endocannabinoid system can protect neurons against glutamate excitotoxicity and acute neuronal damage in both in vitro and in vivo models. In this paper we review the data concerning the involvement of the endocannabinoid system in neurodegenerative diseases in which neuronal cell death may be elicited by excitotoxicity. We focus on the biosynthesis of endocannabinoids and on their modes of action in animal models of these neurodegenerative diseases.
van der Stelt
Mario
M
Department of Bio-organic Chemistry, Bijvoet Center for Biomolecular Science, Padualaan 8, NL-3584 CH Utrecht University, Utrecht, The Netherlands.
Hansen
Henrik H
HH
Veldhuis
Wouter B
WB
Bär
Peter R
PR
Nicolay
Klaas
K
Veldink
Gerrit A
GA
Vliegenthart
Johannes F G
JF
Hansen
Harald S
HS
D000208:Acute Disease; D000818:Animals; D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids / Q000096:biosynthesis / Q000378:metabolism*; D002908:Chronic Disease; D018450:Disease Progression; D063388:Endocannabinoids; D006801:Humans; D019636:Neurodegenerative Diseases / Q000503:physiopathology*; D009435:Synaptic Transmission
D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids; D063388:Endocannabinoids