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Cannabinoid receptors and endocannabinoids: role in neuroinflammatory and neurodegenerative disorders.
CNS Neurol Disord Drug Targets 2010; 9(5):564-73CN

Abstract

The G-protein coupled receptors for Δ⁹-tetrahydrocannabinol, the major psychoactive principle of marijuana, are known as cannabinoid receptors of type 1 (CB₁) and 2 (CB₂) and play important functions in degenerative and inflammatory disorders of the central nervous system. Whilst CB₁ receptors are mostly expressed in neurons, where they regulate neurotransmitter release and synaptic strength, CB₂ receptors are found mostly in glial cells and microglia, which become activated and over-express these receptors during disorders such as Alzheimer's disease, multiple sclerosis, amyotropic lateral sclerosis, Parkinson's disease, and Huntington's chorea. The neuromodulatory actions at CB₁ receptors by endogenous agonists ('endocannabinoids'), of which anandamide and 2-arachidonoylglycerol are the two most studied representatives, allows them to counteract the neurochemical unbalances arising during these disorders. In contrast, the immunomodulatory effects of these lipophilic mediators at CB₂ receptors regulate the activity and function of glia and microglia. Indeed, the level of expression of CB₁ and CB₂ receptors or of enzymes controlling endocannabinoid levels, and hence the concentrations of endocannabinoids, undergo time- and brain region-specific changes during neurodegenerative and neuroinflammatory disorders, with the initial attempt to counteract excitotoxicity and inflammation. Here we discuss this plasticity of the endocannabinoid system during the aforementioned central nervous system disorders, as well as its dysregulation, both of which have opened the way to the use of either direct and indirect activators or blockers of CB₁ and CB₂ receptors for the treatment of the symptoms or progression of these diseases.

Authors+Show Affiliations

Institute of Biomolecular Chemistry, National Research Council, Pozzuoli, Naples, Italy.No affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

20632970

Citation

Bisogno, Tiziana, and Vincenzo Di Marzo. "Cannabinoid Receptors and Endocannabinoids: Role in Neuroinflammatory and Neurodegenerative Disorders." CNS & Neurological Disorders Drug Targets, vol. 9, no. 5, 2010, pp. 564-73.
Bisogno T, Di Marzo V. Cannabinoid receptors and endocannabinoids: role in neuroinflammatory and neurodegenerative disorders. CNS Neurol Disord Drug Targets. 2010;9(5):564-73.
Bisogno, T., & Di Marzo, V. (2010). Cannabinoid receptors and endocannabinoids: role in neuroinflammatory and neurodegenerative disorders. CNS & Neurological Disorders Drug Targets, 9(5), pp. 564-73.
Bisogno T, Di Marzo V. Cannabinoid Receptors and Endocannabinoids: Role in Neuroinflammatory and Neurodegenerative Disorders. CNS Neurol Disord Drug Targets. 2010;9(5):564-73. PubMed PMID: 20632970.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cannabinoid receptors and endocannabinoids: role in neuroinflammatory and neurodegenerative disorders. AU - Bisogno,Tiziana, AU - Di Marzo,Vincenzo, PY - 2010/02/25/received PY - 2010/02/25/accepted PY - 2010/7/17/entrez PY - 2010/7/17/pubmed PY - 2011/3/2/medline SP - 564 EP - 73 JF - CNS & neurological disorders drug targets JO - CNS Neurol Disord Drug Targets VL - 9 IS - 5 N2 - The G-protein coupled receptors for Δ⁹-tetrahydrocannabinol, the major psychoactive principle of marijuana, are known as cannabinoid receptors of type 1 (CB₁) and 2 (CB₂) and play important functions in degenerative and inflammatory disorders of the central nervous system. Whilst CB₁ receptors are mostly expressed in neurons, where they regulate neurotransmitter release and synaptic strength, CB₂ receptors are found mostly in glial cells and microglia, which become activated and over-express these receptors during disorders such as Alzheimer's disease, multiple sclerosis, amyotropic lateral sclerosis, Parkinson's disease, and Huntington's chorea. The neuromodulatory actions at CB₁ receptors by endogenous agonists ('endocannabinoids'), of which anandamide and 2-arachidonoylglycerol are the two most studied representatives, allows them to counteract the neurochemical unbalances arising during these disorders. In contrast, the immunomodulatory effects of these lipophilic mediators at CB₂ receptors regulate the activity and function of glia and microglia. Indeed, the level of expression of CB₁ and CB₂ receptors or of enzymes controlling endocannabinoid levels, and hence the concentrations of endocannabinoids, undergo time- and brain region-specific changes during neurodegenerative and neuroinflammatory disorders, with the initial attempt to counteract excitotoxicity and inflammation. Here we discuss this plasticity of the endocannabinoid system during the aforementioned central nervous system disorders, as well as its dysregulation, both of which have opened the way to the use of either direct and indirect activators or blockers of CB₁ and CB₂ receptors for the treatment of the symptoms or progression of these diseases. SN - 1996-3181 UR - https://www.unboundmedicine.com/medline/citation/20632970/Cannabinoid_receptors_and_endocannabinoids:_role_in_neuroinflammatory_and_neurodegenerative_disorders_ L2 - http://www.eurekaselect.com/94022/article DB - PRIME DP - Unbound Medicine ER -