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A further update on the role of excitotoxicity in the pathogenesis of Parkinson’s disease

  • Neurology and Preclinical Neurological Studies - Review article
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Abstract

Increased levels of extracellular glutamate and hyperactivation of glutamatergic receptors in the basal ganglia trigger a critical cascade of events involving both intracellular pathways and cell-to-cell interactions that affect cell viability and promote neuronal death. The ensemble of these glutamate-triggered events is responsible for excitotoxicity, a phenomenon involved in several pathological conditions affecting the central nervous system, including a neurodegenerative disease such as Parkinson’s disease (PD). PD is an age-related disorder caused by the degeneration of dopaminergic neurons within the substantia nigra pars compacta, with a miscellaneous pathogenic background. Glutamate-mediated excitotoxicity may be involved in a lethal vicious cycle, which critically contributes to the exacerbation of nigrostriatal degeneration in PD. Since excitotoxicity is a glutamate-receptor-mediated phenomenon, growing interest and work have been dedicated to the research for modulators of glutamate neurotransmission that might enable new therapeutic interventions to slow down the neurodegenerative process and ameliorate PD motor symptoms.

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Authors and Affiliations

  1. Laboratory of Functional Neurochemistry, Center for Research in Neurodegenerative Diseases, National Neurological Institute C. Mondino, Via Mondino 2, 27100, Pavia, Italy

    Giulia Ambrosi, Silvia Cerri & Fabio Blandini

  2. Department of Brain and Behavioral Sciences, University of Pavia, Via Ferrata 9, 27100, Pavia, Italy

    Giulia Ambrosi

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  1. Giulia Ambrosi
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  2. Silvia Cerri
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  3. Fabio Blandini
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Correspondence to Fabio Blandini.

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Ambrosi, G., Cerri, S. & Blandini, F. A further update on the role of excitotoxicity in the pathogenesis of Parkinson’s disease. J Neural Transm 121, 849–859 (2014). https://doi.org/10.1007/s00702-013-1149-z

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  • DOI: https://doi.org/10.1007/s00702-013-1149-z

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