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Endocannabinoid system: emerging role from neurodevelopment to neurodegeneration.

Abstract

The endocannabinoid system, including endogenous ligands ('endocannabinoids' ECs), their receptors, synthesizing and degrading enzymes, as well as transporter molecules, has been detected from the earliest stages of embryonic development and throughout pre- and postnatal development. ECs are bioactive lipids, which comprise amides, esters and ethers of long chain polyunsaturated fatty acids. Anandamide (N-arachidonoylethanolamine; AEA) and 2-arachidonoylglycerol (2-AG) are the best studied ECs, and act as agonists of cannabinoid receptors. Thus, AEA and 2-AG mimic several pharmacological effects of the exogenous cannabinoid delta9-tetrahydrocannabinol (Delta(9)-THC), the psychoactive principle of cannabis sativa preparations like hashish and marijuana. Recently, however, several lines of evidence have suggested that the EC system may play an important role in early neuronal development as well as a widespread role in neurodegeneration disorders. Many of the effects of cannabinoids and ECs are mediated by two G protein-coupled receptors (GPCRs), CB1 and CB2, although additional receptors may be implicated. Both CB1 and CB2 couple primarily to inhibitory G proteins and are subject to the same pharmacological influences as other GPCRs. This new system is briefly presented in this review, in order to put in a better perspective the role of the EC pathway from neurodevelopment to neurodegenerative disorders, like Alzheimer's disease, Parkinson's disease, Huntington's disease, and multiple sclerosis. In addition, the potential exploitation of antagonists of CB1 receptors, or of inhibitors of EC metabolism, as next-generation therapeutics is discussed.

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  • Authors+Show Affiliations

    ,

    Center for Dementia Research, Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Rd, Orangeburg, NY 10962, USA. Basavaraj@nki.rfmh.org

    ,

    Source

    MeSH

    Animals
    Brain
    Cannabinoid Receptor Antagonists
    Cannabinoid Receptor Modulators
    Drug Discovery
    Endocannabinoids
    Humans
    Mental Disorders
    Models, Biological
    Nervous System
    Neurodegenerative Diseases
    Receptor, Cannabinoid, CB1
    Receptors, Cannabinoid
    Signal Transduction

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural
    Review

    Language

    eng

    PubMed ID

    19356123

    Citation

    Basavarajappa, Balapal S., et al. "Endocannabinoid System: Emerging Role From Neurodevelopment to Neurodegeneration." Mini Reviews in Medicinal Chemistry, vol. 9, no. 4, 2009, pp. 448-62.
    Basavarajappa BS, Nixon RA, Arancio O. Endocannabinoid system: emerging role from neurodevelopment to neurodegeneration. Mini Rev Med Chem. 2009;9(4):448-62.
    Basavarajappa, B. S., Nixon, R. A., & Arancio, O. (2009). Endocannabinoid system: emerging role from neurodevelopment to neurodegeneration. Mini Reviews in Medicinal Chemistry, 9(4), pp. 448-62.
    Basavarajappa BS, Nixon RA, Arancio O. Endocannabinoid System: Emerging Role From Neurodevelopment to Neurodegeneration. Mini Rev Med Chem. 2009;9(4):448-62. PubMed PMID: 19356123.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Endocannabinoid system: emerging role from neurodevelopment to neurodegeneration. AU - Basavarajappa,Balapal S, AU - Nixon,Ralph A, AU - Arancio,Ottavio, PY - 2009/4/10/entrez PY - 2009/4/10/pubmed PY - 2009/6/24/medline SP - 448 EP - 62 JF - Mini reviews in medicinal chemistry JO - Mini Rev Med Chem VL - 9 IS - 4 N2 - The endocannabinoid system, including endogenous ligands ('endocannabinoids' ECs), their receptors, synthesizing and degrading enzymes, as well as transporter molecules, has been detected from the earliest stages of embryonic development and throughout pre- and postnatal development. ECs are bioactive lipids, which comprise amides, esters and ethers of long chain polyunsaturated fatty acids. Anandamide (N-arachidonoylethanolamine; AEA) and 2-arachidonoylglycerol (2-AG) are the best studied ECs, and act as agonists of cannabinoid receptors. Thus, AEA and 2-AG mimic several pharmacological effects of the exogenous cannabinoid delta9-tetrahydrocannabinol (Delta(9)-THC), the psychoactive principle of cannabis sativa preparations like hashish and marijuana. Recently, however, several lines of evidence have suggested that the EC system may play an important role in early neuronal development as well as a widespread role in neurodegeneration disorders. Many of the effects of cannabinoids and ECs are mediated by two G protein-coupled receptors (GPCRs), CB1 and CB2, although additional receptors may be implicated. Both CB1 and CB2 couple primarily to inhibitory G proteins and are subject to the same pharmacological influences as other GPCRs. This new system is briefly presented in this review, in order to put in a better perspective the role of the EC pathway from neurodevelopment to neurodegenerative disorders, like Alzheimer's disease, Parkinson's disease, Huntington's disease, and multiple sclerosis. In addition, the potential exploitation of antagonists of CB1 receptors, or of inhibitors of EC metabolism, as next-generation therapeutics is discussed. SN - 1389-5575 UR - https://www.unboundmedicine.com/medline/citation/19356123/Endocannabinoid_system:_emerging_role_from_neurodevelopment_to_neurodegeneration_ L2 - http://www.eurekaselect.com/84159/article DB - PRIME DP - Unbound Medicine ER -