Neurochemical Research

, Volume 32, Issue 4–5, pp 757–773 | Cite as

Redox Regulation of Cellular Stress Response in Aging and Neurodegenerative Disorders: Role of Vitagenes

  • Vittorio CalabreseEmail author
  • Eleonora Guagliano
  • Maria Sapienza
  • Mariangela Panebianco
  • Stella Calafato
  • Edoardo Puleo
  • Giovanni Pennisi
  • Cesare Mancuso
  • D. Allan Butterfield
  • Annamaria Giuffrida Stella
Original Paper


Reduced expression and/or activity of antioxidant proteins lead to oxidative stress, accelerated aging and neurodegeneration. However, while excess reactive oxygen species (ROS) are toxic, regulated ROS play an important role in cell signaling. Perturbation of redox status, mutations favoring protein misfolding, altered glyc(osyl)ation, overloading of the product of polyunsaturated fatty acid peroxidation (hydroxynonenals, HNE) or cholesterol oxidation, can disrupt redox homeostasis. Collectively or individually these effects may impose stress and lead to accumulation of unfolded or misfolded proteins in brain cells. Alzheimer’s (AD), Parkinson’s and Huntington’s disease, amyotrophic lateral sclerosis and Friedreich’s ataxia are major neurological disorders associated with production of abnormally aggregated proteins and, as such, belong to the so-called “protein conformational diseases”. The pathogenic aggregation of proteins in non-native conformation is generally associated with metabolic derangements and excessive production of ROS. The “unfolded protein response” has evolved to prevent accumulation of unfolded or misfolded proteins. Recent discoveries of the mechanisms of cellular stress signaling have led to new insights into the diverse processes that are regulated by cellular stress responses. The brain detects and overcomes oxidative stress by a complex network of “longevity assurance processes” integrated to the expression of genes termed vitagenes. Heat-shock proteins are highly conserved and facilitate correct protein folding. Heme oxygenase-1, an inducible and redox-regulated enzyme, has having an important role in cellular antioxidant defense. An emerging concept is neuroprotection afforded by heme oxygenase by its heme degrading activity and tissue-specific antioxidant effects, due to its products carbon monoxide and biliverdin, which is then reduced by biliverdin reductase in bilirubin. There is increasing interest in dietary compounds that can inhibit, retard or reverse the steps leading to neurodegeneration in AD. Specifically any dietary components that inhibit inappropriate inflammation, AβP oligomerization and consequent increased apoptosis are of particular interest, with respect to a chronic inflammatory response, brain injury and β-amyloid associated pathology. Curcumin and ferulic acid, the first from the curry spice turmeric and the second a major constituent of fruit and vegetables, are candidates in this regard. Not only do these compounds serve as antioxidants but, in addition, they are strong inducers of the heat-shock response. Food supplementation with curcumin and ferulic acid are therefore being considered as a novel nutritional approach to reduce oxidative damage and amyloid pathology in AD. We review here some of the emerging concepts of pathways to neurodegeneration and how these may be overcome by a nutritional approach.


Free radicals Oxidant/antioxidant balance Stress response Heme oxygenase Alzheimer's disease 



This work was supported by grants of Italian Cofin 2000, FIRB RBNE01ZK8F, and by NIH grants to D.A.B. [AG-05119; AG-10836].


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Copyright information

© Springer Science+Business Media, LLC 2006

Authors and Affiliations

  • Vittorio Calabrese
    • 1
    Email author
  • Eleonora Guagliano
    • 1
  • Maria Sapienza
    • 1
  • Mariangela Panebianco
    • 1
  • Stella Calafato
    • 1
  • Edoardo Puleo
    • 1
  • Giovanni Pennisi
    • 2
  • Cesare Mancuso
    • 3
  • D. Allan Butterfield
    • 4
  • Annamaria Giuffrida Stella
    • 1
  1. 1.Section of Biochemistry and Molecular Biology, Department of Chemistry, Faculty of Medicine University of CataniaCataniaItaly
  2. 2.Department of Neurosciences, Faculty of Medicine University of CataniaCataniaItaly
  3. 3.Institute of PharmacologyCatholic University School of MedicineRomeItaly
  4. 4.Department of Chemistry, Sanders-Brown Center on Aging and Center of Membrane SciencesUniversity of KentuckyLexingtonUSA

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