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

Giulia Ambrosi, Silvia Cerri, Fabio Blandini

Research output: Contribution to journalArticle

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-receptormediated 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.

Original languageEnglish
Pages (from-to)849-859
Number of pages11
JournalJournal of Neural Transmission
Volume121
Issue number8
DOIs
Publication statusPublished - Jan 1 2014

Keywords

  • Calcium
  • Excitotoxicity
  • Glutamate receptors
  • Metabolic shift
  • NMDARs and mGluR5 antagonists

ASJC Scopus subject areas

  • Biological Psychiatry
  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Medicine(all)

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