Abstract: Mitochondrial dysfunction may be a principal underlying event in aging, including age-associated brain degeneration. Mitochondria provide energy for basic metabolic processes. Their decay with age impairs cellular metabolism and leads to a decline of cellular function. Alzheimer disease (AD) and cerebrovascular accidents (CVAs) are two leading causes of age-related dementia. Increasing evidence strongly supports the theory that oxidative stress, largely due to reactive oxygen species (ROS), induces mitochondrial damage, which arises from chronic hypoperfusion and is primarily responsible for the pathogenesis that underlies both disease processes. Mitochondrial membrane potential, respiratory control ratios and cellular oxygen consumption decline with age and correlate with increased oxidant production. The sustained hypoperfusion and oxidative stress in brain tissues can stimulate the expression of nitric oxide synthases (NOSs) and brain endothelium probably increase the accumulation of oxidative stress products, which therefore contributes to blood brain barrier (BBB) breakdown and brain parenchymal cell damage. Determining the mechanisms behind these imbalances may provide crucial information in the development of new, more effective therapies for stroke and AD patients in the near future.
Keywords: oxidative stress; Alzheimer disease; antioxidants; hypometabolism; mitochondria; metabolism; neurodegeneration
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Aliev, G.; Palacios, H.H.; Gasimov, E.; Obrenovich, M.E.; Morales, L.; Leszek, J.; Bragin, V.; Solís Herrera, A.; Gokhman, D. Oxidative Stress Induced Mitochondrial Failure and Vascular Hypoperfusion as a Key Initiator for the Development of Alzheimer Disease. Pharmaceuticals 2010, 3, 158-187.
Aliev G, Palacios HH, Gasimov E, Obrenovich ME, Morales L, Leszek J, Bragin V, Solís Herrera A, Gokhman D. Oxidative Stress Induced Mitochondrial Failure and Vascular Hypoperfusion as a Key Initiator for the Development of Alzheimer Disease. Pharmaceuticals. 2010; 3(1):158-187.
Aliev, Gjumrakch; Palacios, Hector H.; Gasimov, Eldar; Obrenovich, Mark E.; Morales, Ludis; Leszek, Jerzy; Bragin, Valentin; Solís Herrera, Arturo; Gokhman, Dmitry. 2010. "Oxidative Stress Induced Mitochondrial Failure and Vascular Hypoperfusion as a Key Initiator for the Development of Alzheimer Disease." Pharmaceuticals 3, no. 1: 158-187.