IMR Press / FBL / Volume 12 / Issue 3 / DOI: 10.2741/2130

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Mitochondrial dysfunction, free radical generation and cellular stress response in neurodegenerative disorders
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1 Institute of Pharmacology, Catholic University School of Medicine, Rome, Italy
2 Department of Chemistry, Biochemistry and Mol. Biology Section, Faculty of Medicine, University of Catania, Catania, Italy
3 Department of Biochemical Sciences, University of Rome "La Sapienza," Rome, Italy
4 Department of Chemistry, Sanders-Brown Center on Aging and Center of Membrane Sciences, University of Kentucky, Lexington, Kentucky, USA
Academic Editors:Alberto Boveris, Ana Navarro
Front. Biosci. (Landmark Ed) 2007, 12(3), 1107–1123; https://doi.org/10.2741/2130
Published: 1 January 2007
(This article belongs to the Special Issue Mitochondria: physiological function, signaling and oxidative damage)
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 neuro-inflammation 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.

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