Oxidative stress, protein modification and Alzheimer disease.
Alzheimer disease (AD) is a progressive neurodegenerative disease that affects the elderly population with complex etiology. Many hypotheses have been proposed to explain different causes of AD, but the exact mechanisms remain unclear. In this review, we focus attention on the oxidative-stress hypothesis of neurodegeneration and we discuss redox proteomics approaches to analyze post-mortem human brain from AD brain. Collectively, these studies have provided valuable insights into the molecular mechanisms involved both in the pathogenesis and progression of AD, demonstrating the impairment of numerous cellular processes such as energy production, cellular structure, signal transduction, synaptic function, mitochondrial function, cell cycle progression, and degradative systems. Each of these cellular functions normally contributes to maintain healthy neuronal homeostasis, so the deregulation of one or more of these functions could contribute to the pathology and clinical presentation of AD. In particular, we discuss the evidence demonstrating the oxidation/dysfunction of a number of enzymes specifically involved in energy metabolism that support the view that reduced glucose metabolism and loss of ATP are crucial events triggering neurodegeneration and progression of AD.
Department of Biochemical Sciences, Sapienza University of Rome, 00185 Rome, Italy.
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Tramutola
Department of Biochemical Sciences, Sapienza University of Rome, 00185 Rome, Italy.
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Lanzillotta
Department of Biochemical Sciences, Sapienza University of Rome, 00185 Rome, Italy.
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Perluigi
Department of Chemistry and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40506, USA. Electronic address: dabcns@uky.edu.
D Allan
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Butterfield
D000544:Alzheimer Disease / Q000378:metabolism* / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D025261:Mitochondrial Proton-Translocating ATPases / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology; D011499:Protein Processing, Post-Translational / Q000502:physiology; D059748:Proteolysis; D040901:Proteomics / Q000379:methods; D017382:Reactive Oxygen Species / Q000378:metabolism
D016229:Amyloid beta-Peptides; D017382:Reactive Oxygen Species; D025261:Mitochondrial Proton-Translocating ATPases; D005947:Glucose
ATP synthase; Alzheimer disease; Glucose metabolism; Oxidative stress; Protein oxidation