Pathogenesis of Alzheimer Disease: Role of Oxidative Stress, Amyloid-β Peptides, Systemic Ammonia and Erythrocyte Energy Metabolism
Elena A. Kosenko, Iliya N. Solomadin, Lyudmila A. Tikhonova, V. Prakash Reddy, Gjumrakch Aliev and Yury G. Kaminsky
Affiliation: (Gjumrakch Aliev) GALLY International Biomedical Research Institute Inc., 7733 Louis Pasteur Drive, #328, San Antonio, TX, 78229, USA.
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.
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