Affiliations: [a] Chongqing Key Laboratory of Neurodegenerative Diseases, Chongqing, China
| [b]
Department of Neurology, Chongqing General Hospital, University of Chinese Academy of Sciences, Chongqing, China
| [c]
Zunyi Medical University, Zunyi, China
Correspondence:
[*]
Correspondence to: Zhi-You Cai, Department of Neurology, Chongqing General Hospital, University of Chinese Academy of Sciences, No. 312 Zhongshan First Road, Yuzhong District, Chongqing 400013, People’s Republic of China. Tel.: +86 23 63515796; Fax: +86 23 63515796; E-mail: [email protected].
Abstract: Amyloid-β (Aβ) 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-1α (HIF-1α) is a transcriptional factor responsible for cellular and tissue adaption to low oxygen tension. Emerging evidence has revealed HIF-1α as a potential medicinal target for neurodegenerative diseases. On the one hand, HIF-1α increases AβPP processing and Aβ generation by promoting β/γ-secretases and suppressing α-secretases, inactivates microglia and reduces their activity, contributes to microglia death and neuroinflammation, which promotes AD pathogenesis. On the other hand, HIF-1α could resist the toxic effect of Aβ, inhibits tau hyperphosphorylation and promotes microglial activation. In summary, this review focuses on the potential complex roles and the future perspectives of HIF-1α in AD, in order to provide references for seeking new drug targets and treatment methods for AD.
Keywords: Alzheimer’s disease, amyloid-β, HIF-1α, neuroinflammation, oxidative stress, tau hyperphosphorylation
