Hypoxia, Oxidative Stress and Inflammation Three faces of neurodegenerative diseases

MERELLI A; AUZMENDI J; LAZAROWSKI A; REPETTO, M

JOURNAL OF ALZHEIMER'S DISEASE

IOS PRESS

Lugar: Amsterdam; Año: 2020 p. 1 - 18

1387-2877

The cerebral hypoxia-ischemia can induce a wide spectrum of biologic responses that include depolarization, excitotoxicity, oxidative stress, inflammation, and apoptosis, and resulting in neurodegeneration. Several adaptive and survival endogenous mechanisms can also be activated giving an opportunity to the affected cells of remain alive, waiting the helper signals that avoid the apoptosis. These signals will come up to help the cells, depending on intensity, chronicity and proximity to the central hypoxic area of the affected tissue. These mechanisms are present in a large list of commonly brain pathologies affecting older individuals, and others such as refractory epilepsies, encephalopathies or brain trauma, where mentioned neurodegenerative process with cognitive and/or motor deficits sequelae is observed. The hypoxia inducible factor 1 (HIF-1), is a master transcription factor driving a wide spectrum cellular responses. HIF-1 can induce the overexpression of the erythropoietin receptor (EPO-R), that provides the opportunity to administer pharmacological doses of erythropoietin (EPO), increasing the chances of rescue and repair the brain tissue affected. Intranasal way of EPO administration combined with other antioxidant and anti-inflammatory compounds could become a therapeutic alternative, to avoid and/or slow down the progressive deterioration that characterizes neurodegeneration, without peripheral adverse effects.