Prospects for cannabinoid therapies in basal ganglia disorders

Authors

  • Javier Fernández-Ruiz,

    Corresponding author
    1. Departamento de Bioquímica y Biología Molecular III, Instituto Universitario de Investigación en Neuroquímica, Facultad de Medicina, Universidad Complutense, Madrid, Spain
    2. Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
    3. Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
      Javier Fernández-Ruiz, Departamento de Bioquímica y Biología Molecular III, Facultad de Medicina, Universidad Complutense, Ciudad Universitaria s/n, 28040 Madrid, Spain. E-mail: jjfr@med.ucm.es
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  • Miguel Moreno-Martet,

    1. Departamento de Bioquímica y Biología Molecular III, Instituto Universitario de Investigación en Neuroquímica, Facultad de Medicina, Universidad Complutense, Madrid, Spain
    2. Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
    3. Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
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  • Carmen Rodríguez-Cueto,

    1. Departamento de Bioquímica y Biología Molecular III, Instituto Universitario de Investigación en Neuroquímica, Facultad de Medicina, Universidad Complutense, Madrid, Spain
    2. Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
    3. Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
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  • Cristina Palomo-Garo,

    1. Departamento de Bioquímica y Biología Molecular III, Instituto Universitario de Investigación en Neuroquímica, Facultad de Medicina, Universidad Complutense, Madrid, Spain
    2. Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
    3. Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
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  • María Gómez-Cañas,

    1. Departamento de Bioquímica y Biología Molecular III, Instituto Universitario de Investigación en Neuroquímica, Facultad de Medicina, Universidad Complutense, Madrid, Spain
    2. Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
    3. Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
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  • Sara Valdeolivas,

    1. Departamento de Bioquímica y Biología Molecular III, Instituto Universitario de Investigación en Neuroquímica, Facultad de Medicina, Universidad Complutense, Madrid, Spain
    2. Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
    3. Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
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  • Carmen Guaza,

    1. Neuroimmunology Group, Functional and Systems Neurobiology Department, Cajal Institute (CSIC), Madrid, Spain
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  • Julián Romero,

    1. Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
    2. Laboratorio de Investigación, Fundación Hospital Alcorcón, Madrid, Spain
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  • Manuel Guzmán,

    1. Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
    2. Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
    3. Departamento de Bioquímica y Biología Molecular I, Instituto Universitario de Investigación en Neuroquímica, Facultad de Biología, Universidad Complutense, Madrid, Spain
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  • Raphael Mechoulam,

    1. Department of Medicinal Chemistry and Natural Products, Medical Faculty, Hebrew University, Jerusalem, Israel
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  • José A Ramos

    1. Departamento de Bioquímica y Biología Molecular III, Instituto Universitario de Investigación en Neuroquímica, Facultad de Medicina, Universidad Complutense, Madrid, Spain
    2. Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
    3. Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
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Javier Fernández-Ruiz, Departamento de Bioquímica y Biología Molecular III, Facultad de Medicina, Universidad Complutense, Ciudad Universitaria s/n, 28040 Madrid, Spain. E-mail: jjfr@med.ucm.es

Abstract

Cannabinoids are promising medicines to slow down disease progression in neurodegenerative disorders including Parkinson's disease (PD) and Huntington's disease (HD), two of the most important disorders affecting the basal ganglia. Two pharmacological profiles have been proposed for cannabinoids being effective in these disorders. On the one hand, cannabinoids like Δ9-tetrahydrocannabinol or cannabidiol protect nigral or striatal neurons in experimental models of both disorders, in which oxidative injury is a prominent cytotoxic mechanism. This effect could be exerted, at least in part, through mechanisms independent of CB1 and CB2 receptors and involving the control of endogenous antioxidant defences. On the other hand, the activation of CB2 receptors leads to a slower progression of neurodegeneration in both disorders. This effect would be exerted by limiting the toxicity of microglial cells for neurons and, in particular, by reducing the generation of proinflammatory factors. It is important to mention that CB2 receptors have been identified in the healthy brain, mainly in glial elements and, to a lesser extent, in certain subpopulations of neurons, and that they are dramatically up-regulated in response to damaging stimuli, which supports the idea that the cannabinoid system behaves as an endogenous neuroprotective system. This CB2 receptor up-regulation has been found in many neurodegenerative disorders including HD and PD, which supports the beneficial effects found for CB2 receptor agonists in both disorders. In conclusion, the evidence reported so far supports that those cannabinoids having antioxidant properties and/or capability to activate CB2 receptors may represent promising therapeutic agents in HD and PD, thus deserving a prompt clinical evaluation.

LINKED ARTICLES This article is part of a themed issue on Cannabinoids in Biology and Medicine. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.163.issue-7

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