Acute neuronal injury,excitotoxicity, and the endocannabinoid system |
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Authors: | van der Stelt Mario Veldhuis Wouter B Maccarrone Mauro Bär Peter R Nicolay Klaas Veldink Gerrit A Di Marzo Vincenzo Vliegenthart Johannes F G |
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Institution: | (1) Department of Bio-Organic Chemistry, Bijvoet Center for Biomolecular Research, Utrecht University, Padualaan 8, NL-3584 CH Utrecht, The Netherlands;(2) Department of Experimental in vivo NMR, Image Sciences Institute, Utrecht, University Medical Center Utrecht, The Netherlands;(3) Department of Experimental Neurology, University Medical Center Utrecht, Utrecht, The Netherlands;(4) Department of Experimental Medicine and Biochemical Sciences, University of Rome “Tor Vergata”, Rome, Italy;(5) Endocannabinoid Research Group, Institute of Biomolecular Chemistry—Consiglio Nazionale delle Ricerche, Pozzuoli (Naples), Italy |
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Abstract: | The endocannabinoid system is a valuable target for drug discovery, because it is involved in the regulation of many cellular
and physiological functions. The endocannabinoid system constitutes the endogenous lipids anandamide, 2-arachidonoylglycerol
and noladin ether, and the cannabinoid CB1 and CB2 receptors as well as the proteins for their inactivation. It is thought that (endo)cannabinoid-based drugs may potentially
be useful to reduce the effects of neurodegeneration. This paper reviews recent developments in the endocannabinoid system
and its involvement in neuroprotection.
Exogenous (endo)cannabinoids have been shown to exert neuroprotection in a variety of in vitro and in vivo models of neuronal
injury via different mechanisms, such as prevention of excitotoxicity by CB1-mediated inhibition of glutamatergic transmission, reduction of calcium influx, and subsequent inhibition of deleterious
cascades, TNF-α formation, and anti-oxidant activity. It has been suggested that the release of endogenous endocannabinoids
during neuronal injury might be a protective response. However, several observations indicate that the role of the endocannabinoid
system as a general endogenous protection system is questionable. The data are critically reviewed and possible explanations
are given. |
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Keywords: | Cannabinoid anandamide 2-arachidonoylglycerol excitotoxicity neuroprotection neurodegeneration |
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