Possible use of adaptation to hypoxia in Alzheimer's disease: a hypothesis.
Disorders in memory and other cognitive functions in Alzheimer's disease (AD) may result from an exhaustion of adaptive reserves in the brain. Therefore it is a challenge to find methods to increase the adaptive reserve of the organism to combat AD. Excitotoxicity, Ca2+ homeostasis disruptions, oxidative stress, disturbed synthesis of NO, and impaired cerebral circulation are suggested as key pathogenic factors of AD. At present it appears that stimulation of the self-defense systems in neural cells is a promising strategy in restricting the progression of AD. These systems include those of antioxidants, heat shock proteins (HSPs), NO, and other so-called stress-limiting systems. Non-drug activation of these systems can be achieved most efficiently by adaptation of the organism to environmental challenges, such as hypoxia. In this paper the potential of methods used in adaptive medicine is explored. The protective mechanisms of adaptation to hypoxia may be related to restriction of oxidative stress in the hippocampus, the limitation of a decrease in NO production induced by beta-amyloid, and increased density of the vascular network in the brain. In this review we selectively present data that support the idea that adaptation to hypoxia is a possible non-drug means in the prevention of AD. In our opinion this strategy may provide a break-through in the clinical approach of this disease.
Malyshev
Igor Yu
IY
Institute of General Pathology and Pathophysiology, Moscow, Russia. igor.malyshev@mtu-net.ru
Wiegant
Frederik A C
FA
Mashina
Svetlana Yu
SY
Torshin
Vladimir I
VI
Goryacheva
Anna V
AV
Khomenko
Inna P
IP
Kruglov
Sergey V
SV
Pokidyshev
Dmitry A
DA
Popkova
Elena V
EV
Pshennikova
Maya G
MG
Vlasova
Mariya A
MA
Zelenina
Olga M
OM
Manukhina
Eugenia B
EB
D000222:Adaptation, Physiological; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D000818:Animals; D002560:Cerebrovascular Circulation; D004777:Environment; D005609:Free Radicals / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D008954:Models, Biological; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism; D010084:Oxidation-Reduction
D005609:Free Radicals; D018840:HSP70 Heat-Shock Proteins; D009569:Nitric Oxide