2. Academic Validation
  3. Targeting Cannabinoid CB2 Receptors in the Central Nervous System. Medicinal Chemistry Approaches with Focus on Neurodegenerative Disorders

Targeting Cannabinoid CB2 Receptors in the Central Nervous System. Medicinal Chemistry Approaches with Focus on Neurodegenerative Disorders

  • Front Neurosci. 2016 Sep 13;10:406. doi: 10.3389/fnins.2016.00406.
Gemma Navarro 1,  Paula Morales 2,  Carmen Rodríguez-Cueto 3,  Javier Fernández-Ruiz 3,  Nadine Jagerovic 4,  Rafael Franco 1
Affiliations

Affiliations

  • 1 Department of Biochemistry and Molecular Biomedicine, University of BarcelonaBarcelona, Spain; Centro de Investigación en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos IIIMadrid, Spain; Cell and Molecular Neuropharmacology, Institut de Biomedicina (IBUB), Universitat de BarcelonaBarcelona, Spain.
  • 2 Instituto de Química Médica, Consejo Superior de Investigaciones CientíficasMadrid, Spain; Center for Drug Discovery, University of North Carolina at GreensboroGreensboro, NC, USA.
  • 3 Centro de Investigación en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos IIIMadrid, Spain; Departamento de Bioquímica, Facultad de Medicina, Instituto Universitario de Investigación en Neuroquímica, Universidad ComplutenseMadrid, Spain; Instituto Ramón y Cajal de Investigación SanitariaMadrid, Spain.
  • 4 Instituto de Química Médica, Consejo Superior de Investigaciones Científicas Madrid, Spain.
PMID: 27679556 DOI: 10.3389/fnins.2016.00406
Abstract

Endocannabinoids activate two types of specific G-protein-coupled receptors (GPCRs), namely cannabinoid CB1 and CB2. Contrary to the psychotropic actions of agonists of CB1 receptors, and serious side effects of the selective antagonists of this receptor, drugs acting on CB2 receptors appear as promising drugs to combat CNS diseases (Parkinson's disease, Huntington's chorea, cerebellar ataxia, amyotrohic lateral sclerosis). Differential localization of CB2 receptors in neural cell types and upregulation in neuroinflammation are keys to understand the therapeutic potential in inter alia diseases that imply progressive neurodegeneration. Medicinal chemistry approaches are now engaged to develop imaging tools to map receptors in the living human brain, to develop more efficacious agonists, and to investigate the possibility to develop allosteric modulators.

Keywords

GPCR; M0/M1/M2 phenotype; amyotrophic lateral sclerosis; astroglia; heteromer; microglia; neuroprotection; neurorestoration.

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