Pathways of neurodegeneration and experimental models of basal ganglia disorders: Downstream effects of mitochondrial inhibition

Massimiliano Di Filippo, Barbara Picconi, Cinzia Costa, Vincenza Bagetta, Michela Tantucci, Lucilla Parnetti, Paolo Calabresi

Research output: Contribution to journalArticle

Abstract

The basal ganglia circuit plays a key role in the regulation of voluntary movements as well as in behavioural control and cognitive functions. The main pathogenic role of mitochondrial dysfunctions is now accepted in the neurodegenerative process and the mitochondria have been successfully used as subcellular targets to obtain relevant experimental models of basal ganglia neurodegenerative disorders. Mitochondrial toxins act through an inhibition of the respiratory chain complexes. These toxins, by uncoupling cellular respiration, shift the cell into a state of oxidative stress and trigger several bidirectional links with the excitotoxic process. Moreover, the in vitro inhibition of the respiratory chain complexes alters the electrophysiological properties of the neurons. The downstream effects triggered by mitochondrial complexes inhibition provide a model integrating genetic and environmental pathogenic factors to explain the selective neuronal vulnerability.

Original languageEnglish
Pages (from-to)65-72
Number of pages8
JournalEuropean Journal of Pharmacology
Volume545
Issue number1
DOIs
Publication statusPublished - Sep 1 2006

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Keywords

  • Basal ganglia
  • Huntington's disease
  • Mitochondria
  • Parkinson's disease

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

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