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Cannabinoids and Neuroprotection in Basal Ganglia Disorders

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Abstract

Cannabinoids have been proposed as clinically promising neuroprotective molecules, as they are capable to reduce excitotoxicity, calcium influx, and oxidative injury. They are also able to decrease inflammation by acting on glial processes that regulate neuronal survival and to restore blood supply to injured area by reducing the vasoconstriction produced by several endothelium-derived factors. Through one or more of these processes, cannabinoids may provide neuroprotection in different neurodegenerative disorders including Parkinson’s disease and Huntington’s chorea, two chronic diseases that are originated as a consequence of the degeneration of specific nuclei of basal ganglia, resulting in a deterioration of the control of movement. Both diseases have been still scarcely explored at the clinical level for a possible application of cannabinoids to delay the progressive degeneration of the basal ganglia. However, the preclinical evidence seems to be solid and promising. There are two key mechanisms involved in the neuroprotection by cannabinoids in experimental models of these two disorders: first, a cannabinoid receptor-independent mechanism aimed at producing a decrease in the oxidative injury and second, an induction/upregulation of cannabinoid CB2 receptors, mainly in reactive microglia, that is capable to regulate the influence of these glial cells on neuronal homeostasis. Considering the relevance of these preclinical data and the lack of efficient neuroprotective strategies in both disorders, we urge the development of further studies that allow that the promising expectatives generated for these molecules progress from the present preclinical evidence till a real clinical application.

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Acknowledgments

The experimental work carried out by our group and that has been mentioned in this review article, has been supported during the last years by the MEC (grants SAF2003-08269 and SAF2006-11333), MSC (CIBERNED, CB06/05/0089) and CAM (S-SAL-0261/2006). The authors are indebted to all colleagues who contributed in this experimental work.

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Authors and Affiliations

  1. Departamento de Bioquímica y Biología Molecular, Facultad de Medicina III, Universidad Complutense, Ciudad Universitaria s/n, 28040, Madrid, Spain

    Onintza Sagredo, Moisés García-Arencibia, Eva de Lago, Simone Finetti, Alessandra Decio & Javier Fernández-Ruiz

  2. CIBER de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, 28029-, Madrid, Spain

    Onintza Sagredo, Moisés García-Arencibia, Eva de Lago & Javier Fernández-Ruiz

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  1. Onintza Sagredo
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  2. Moisés García-Arencibia
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  3. Eva de Lago
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  5. Alessandra Decio
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Correspondence to Javier Fernández-Ruiz.

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Sagredo, O., García-Arencibia, M., de Lago, E. et al. Cannabinoids and Neuroprotection in Basal Ganglia Disorders. Mol Neurobiol 36, 82–91 (2007). https://doi.org/10.1007/s12035-007-0004-3

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