Mitochondrial dysfunction, free radical generation and cellular stress response in neurodegenerative disorders

Cesare Mancuso, Giovanni Scapagnini, Diego Currò, Anna Maria Giuffrida Stella, Carlo De Marco, D. Allan Butterfield, Vittorio Calabrese

Research output: Contribution to journalArticlepeer-review

266 Scopus citations

Abstract

Protein conformational diseases, such as Alzheimer's, Parkinson's and Huntington's, affect a large portion of aging population. The pathogenic dysfunctional aggregation of proteins in non-native conformations is associated with metabolic derangements and excessive production of reactive oxygen species. Reduction of cellular expression and activity of antioxidant proteins result in increased oxidative stress. Free-radicals derived from mitochondrial dysfunction and from the cyclooxygenase enzyme activity play a role in oxidative damage of brain. Cyclooxygenase also mediates in neuroinflammmation by the production of pro-inflammatory prostaglandins which contribute to brain injury. The pathogenic role of cyclooxygenase has been demonstrated in Alzheimer and Parkinson diseases. The brain responses to detect and control diverse forms of stress are accomplished by a complex network of "longevity assurance processes" integrated to the expression of genes termed vitagenes. Heat shock proteins are a highly conserved system responsible for the preservation and repair of correct protein conformation. Heme oxygenase-1, a inducible and redox-regulated enzyme, is currently considered as having an important role in cellular antioxidant defense. A neuroprotective effect, due to its heme degrading activity, and tissue-specific pro-oxidant effects, due to its products CO and free iron, are under debate. There is a current interest in dietary compounds that can inhibit, retard or reverse the multi-stage pathophysiology of Alzheimer disease, with a chronic inflammatory response, brain injury and beta-amyloid associated pathology. Curcumin and ferulic acid, two powerful antioxidants, the first from the curry spice turmeric and the second a major constituent of fruit and vegetables, have emerged as strong inducers of the heat shock response. Food supplementation with curcumin and ferulic acid is considered a nutritional approach to reduce oxidative damage and amyloid pathology in Alzheimer disease.

Original languageEnglish
Pages (from-to)1107-1123
Number of pages17
JournalFrontiers in Bioscience
Volume12
Issue number3
DOIs
StatePublished - 2007

Keywords

  • Alzheimer disease
  • Bilirubin
  • Carbon monoxide
  • Curcumin
  • Cyclooxygenase
  • Heat shock proteins
  • Heme oxygenase-1
  • Mitochondria
  • Oxidative stress
  • Review

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (all)
  • Immunology and Microbiology (all)

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