Aging and Oxidative Stress Response in the CNS
Cellular oxidant/antioxidant balance has become the subject of intense study, particularly focused on brain aging and neurodegenerative disorders. There is now evidence to suggest that reduction of cellular expression and activity of antioxidant proteins
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Aging and Oxidative Stress Response in the CNS
V. Calabrese . D. A. Butterfield . A. M. Giuffrida Stella
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Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104
2 2.1 2.2
The Free‐Radical Hypothesis of Aging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105 The Mitochondrial Theory of Aging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108 Mitochondrial Damage, Reactive Nitrogen Species, and Neurodegenerative Disorders . . . . . . . . 110
3 3.1
Oxidative Stress and Brain Stress Tolerance: Role of Vitagenes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110 Neurogasobiology of Nitric Oxide and Carbon Monoxide: Two Molecules That Promote Adaptive Responses in the CNS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110 3.2 Nitric Oxide Synthase and Its Isoforms in the CNS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111 3.3 Nitric Oxide as a Neurotransmitter . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111 3.4 Redox Activities Elicited by NO . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112 3.5 Regulation of Gene Expression by Oxidative and Nitrosative Stress . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112 3.6 Carbon Monoxide: A Signaling Molecule Endowed with Antiinflammatory Properties . . . . . . . 113 3.7 The Heat‐Shock Pathway of Brain Stress Tolerance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115 3.8 HO System: A Putative Vitagene Target for Neuroprotection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117 3.9 Regulation of HO Genes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118 3.10 Glutathione, Thiol Redox State, and RNS: Intracellular Modulators of HO‐1 Expression . . . . . 119 3.11 Heme Oxygenase in Brain Function and Dysfunction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120 3.12 Bilirubin and Biliverdin: An Endogenous Antioxidant System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121 4 4.1
Caloric Restriction and Endogenous Oxidative Stress: Relevance to Aging and Cell Survival . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122 Therapeutic Potential of Nutritional Antioxidants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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