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Cannabinoid Signaling and Neuroinflammatory Diseases: A Melting pot for the Regulation of Brain Immune Responses

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Abstract

The concept of the central nervous system (CNS) as an immune-privileged site, essentially due to the presence of the blood brain barrier, appears to be overly simplistic. Indeed, within healthy CNS immune activities are permitted and are required for neuronal function and host defense, not only due to the presence of the resident innate immune cells of the brain, but also by virtue of a complex cross-talk of the CNS with peripheral immune cells. Nonetheless, long-standing and persisting neuroinflammatory responses are most often detrimental and characterize several neuroinflammatory diseases, including multiple sclerosis, Alzheimer’s disease and amyotrophic lateral sclerosis. A growing body of evidence suggests that Cannabis sativa-derived phytocannabinoids, as well as synthetic cannabinoids, are endowed with significant immunoregulatory and anti-inflammatory properties, both in peripheral tissues and in the CNS, through the activation of cannabinoid receptors. In this review, the immunomodulatory effects of cannabinoid signaling on the most relevant brain immune cells will be discussed. In addition, the impact of cannabinoid regulation on the overall integration of the manifold brain immune responses will also be highlighted, along with the implication of these compounds as potential agents for the management of neuroinflammatory disorders.

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Acknowledgments

We apologize in advance to all investigators whose research could not be appropriately cited owing to space limitations. We wish to thank Professor Alessandro Finazzi Agrò and Professor Giorgio Bernardi for their continuing support to our studies on cannabinoid signaling. Financial support from Fondazione Italiana Sclerosi Multipla (FISM grant 2013/R/8) to V.C., and from Ministero dell’Istruzione, dell’Università e della Ricerca (PRIN grant 2010–2011) to M.M. is gratefully acknowledged.

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  1. School of Medicine and Center of Integrated Research, Campus Bio-Medico University of Rome, via Alvaro del Portillo 21, 00128, Rome, Italy

    Valerio Chiurchiù, Alessandro Leuti & Mauro Maccarrone

  2. European Center for Brain Research (CERC), I.R.C.C.S. Santa Lucia Foundation, Rome, Italy

    Valerio Chiurchiù, Alessandro Leuti & Mauro Maccarrone

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  1. Valerio Chiurchiù
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Correspondence to Mauro Maccarrone.

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Chiurchiù, V., Leuti, A. & Maccarrone, M. Cannabinoid Signaling and Neuroinflammatory Diseases: A Melting pot for the Regulation of Brain Immune Responses. J Neuroimmune Pharmacol 10, 268–280 (2015). https://doi.org/10.1007/s11481-015-9584-2

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