Abstract
Aβ exerts prooxidant or antioxidant effects based on the metal ion concentrations that it sequesters from the cytosol; at low metal ion concentrations, it is an antioxidant, whereas at relatively higher concentration it is a prooxidant. Thus Alzheimer disease (AD) treatment strategies based solely on the amyloid-β clearance should be re-examined in light of the vast accumulating evidence that increased oxidative stress in the human brains is the key causative factor for AD. Accumulating evidence indicates that the reduced brain glucose availability and brain hypoxia, due to the relatively lower concentration of ATP and 2,3-diphosphoglycerate, may be associated with increased concentration of endogenous ammonia, a potential neurotoxin in the AD brains. In this review, we summarize the progress in this area, and present some of our ongoing research activities with regard to brain Amyloid-β, systemic ammonia, erythrocyte energy metabolism and the role of 2,3-diphosphoglycerate in AD pathogenesis.
Keywords: Alzheimer disease, ammonia, amyloid-β, erythrocyte energy metabolism, oxidative stress.
CNS & Neurological Disorders - Drug Targets
Title:Pathogenesis of Alzheimer Disease: Role of Oxidative Stress, Amyloid-β Peptides, Systemic Ammonia and Erythrocyte Energy Metabolism
Volume: 13 Issue: 1
Author(s): Elena A. Kosenko, Iliya N. Solomadin, Lyudmila A. Tikhonova, V. Prakash Reddy, Gjumrakch Aliev and Yury G. Kaminsky
Affiliation:
Keywords: Alzheimer disease, ammonia, amyloid-β, erythrocyte energy metabolism, oxidative stress.
Abstract: Aβ exerts prooxidant or antioxidant effects based on the metal ion concentrations that it sequesters from the cytosol; at low metal ion concentrations, it is an antioxidant, whereas at relatively higher concentration it is a prooxidant. Thus Alzheimer disease (AD) treatment strategies based solely on the amyloid-β clearance should be re-examined in light of the vast accumulating evidence that increased oxidative stress in the human brains is the key causative factor for AD. Accumulating evidence indicates that the reduced brain glucose availability and brain hypoxia, due to the relatively lower concentration of ATP and 2,3-diphosphoglycerate, may be associated with increased concentration of endogenous ammonia, a potential neurotoxin in the AD brains. In this review, we summarize the progress in this area, and present some of our ongoing research activities with regard to brain Amyloid-β, systemic ammonia, erythrocyte energy metabolism and the role of 2,3-diphosphoglycerate in AD pathogenesis.
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Kosenko A. Elena, Solomadin N. Iliya, Tikhonova A. Lyudmila, Reddy Prakash V., Aliev Gjumrakch and Kaminsky G. Yury, Pathogenesis of Alzheimer Disease: Role of Oxidative Stress, Amyloid-β Peptides, Systemic Ammonia and Erythrocyte Energy Metabolism, CNS & Neurological Disorders - Drug Targets 2014; 13 (1) . https://dx.doi.org/10.2174/18715273113126660130
DOI https://dx.doi.org/10.2174/18715273113126660130 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
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