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Biosynthesis of endocannabinoids and their modes of action in neurodegenerative diseases

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Abstract

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 bothin vitro andin 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.

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Authors and Affiliations

  1. Department of Bio-organic Chemistry, Bijvoet Center for Biomolecular Science, CH Utrecht University, Padualaan 8, NL-3584, Utrecht, The Netherland

    Mario van der Stelt & Gerrit A. Veldink

  2. Department of Pharmacology, The Royal Danish School of Pharmacy, Universitetsparken 2, DK 2100, Copenhagen, Denmark

    Henrik H. Hansen & Harald S. Hansen

  3. Department of Pediatric Neurology, The Charité-Virchow Clinics, Humboldt University, Berlin, Germany

    Henrik H. Hansen

  4. Department of Experimental In Vivo NMR, Image Sciences Institute, Utrecht University Medical Center, Utrecht, The Netherlands

    Wouter B. Veldhuis & Klaas Nicolay

  5. Department of Experimental Neurology, University Medical Center Utrecht, Utrecht, The Netherlands

    Wouter B. Veldhuis & Peter R. Bär

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  1. Mario van der Stelt
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  3. Wouter B. Veldhuis
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  7. Johannes F. G. Vliegenthart
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Correspondence to Gerrit A. Veldink or Harald S. Hansen.

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Both authors contributed equally to the work.

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van der Stelt, M., Hansen, H.H., Veldhuis, W.B. et al. Biosynthesis of endocannabinoids and their modes of action in neurodegenerative diseases. neurotox res 5, 183–199 (2003). https://doi.org/10.1007/BF03033139

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