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Interplay of cannabinoid 2 (CB2) receptors with nitric oxide synthases, oxidative and nitrative stress, and cell death during remote neurodegeneration

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Abstract

Remote neuronal degeneration and death/injury, which often occur in regions remote but functionally connected to the primary lesion site, may play a pivotal role in extending neuronal damage/dysfunction following traumatic brain injury, stroke, or peripheral nerve injury, as well as in chronic neurodegenerative diseases such as multiple sclerosis and amyotrophic lateral sclerosis. Even though the precise mechanisms of remote neuronal injury are poorly understood and no efficacious treatment options are available, it involves glial activation, inflammation, oxidative/nitrative stress, and apoptotic cell death. The newly discovered endocannabinoid signaling system consisting of endocannabinoids (endogenous bioactive lipid mediators), their synthetic and metabolizing enzymes, and their primary G protein-coupled cannabinoid 1 and 2 (CB1 and CB2) receptors has been implicated in the regulation of numerous physiological and pathological processes/functions, including those associated with neurodegeneration. Using a well-characterized rodent model of remote neuronal degeneration, Oddi et al. (J Mol Med 2012, in press, DOI 10.1007/s00109-012-0884-1) have demonstrated that targeting CB2 cannabinoid receptors may represent a promising novel approach to attenuate this pathological process. This editorial discusses the clinical significance of these interesting observations and the mechanisms of the possible interplay of CB2 receptors with nitric oxide synthases, oxidative and nitrative stress, and cell death during remote neurodegeneration.

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Authors and Affiliations

  1. Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA

    Pál Pacher

  2. Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, USA

    Ken Mackie

  3. Section on Oxidative Stress Tissue Injury, Laboratory of Physiological Studies, National Institutes of Health/NIAAA, 5625 Fishers Lane, MSC-9413, Bethesda, MD, 20892-9413, USA

    Pál Pacher

Authors
  1. Pál Pacher
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  2. Ken Mackie
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Corresponding author

Correspondence to Pál Pacher.

Additional information

This work is an editorial on “Distinct regulation of nNOS and iNOS by CB2 receptor in remote delayed neurodegeneration,” by Oddi S, Latini L, Viscomi MT, Bisicchia E, Molinari M, and Maccarrone M (2012) J Mol Med (in press), DOI 10.1007/s00109-011-0846-z.

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Pacher, P., Mackie, K. Interplay of cannabinoid 2 (CB2) receptors with nitric oxide synthases, oxidative and nitrative stress, and cell death during remote neurodegeneration. J Mol Med 90, 347–351 (2012). https://doi.org/10.1007/s00109-012-0884-1

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  • DOI: https://doi.org/10.1007/s00109-012-0884-1

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