Role of Hypoxia Inducible Factor 1a in Alzheimer's Disease.
Amyloid b (Ab) peptides and hyperphosphorylated tau protein are the most important pathological markers of Alzheimer's disease (AD) Neuroinflammation and oxidative stress are also involved in the development and pathological mechanism of AD. Hypoxia inducible factor 1a (HIF 1a) is a transcriptional factor responsible for cellular and tissue adaption to low oxygen tension. Emerging evidence has revealed HIF 1a as a potential medicinal target for neurodegenerative diseases. On the one hand, HIF 1a increases AbPP processing and Ab generation by promoting b/g secretases and suppressing a secretases, inactivates microglia and reduces their activity, contributes to microglia death and neuroinflammation, which promotes AD pathogenesis. On the other hand, HIF 1a could resist the toxic effect of Ab, inhibits tau hyperphosphorylation and promotes microglial activation. In summary, this review focuses on the potential complex roles and the future perspectives of HIF 1a in AD, in order to provide references for seeking new drug targets and treatment methods for AD.
Journal of Alzheimer's disease JAD