文献类型：期刊文献

英文题名：HIF-1α serves as a co-linker between AD and T2DM

作者：Hai, Yang[1,4];Ren, Ke[2];Zhang, Yarong[2];Yang, Lili[2];Cao, Haoshi[2];Yuan, Xianxia[2];Su, Linling[2];Li, Hailong[3];Feng, Xiaoli[1,4];Liu, Dongling[2,5,6,7]

第一作者：杨海

通信作者：Hai, Y[1];Liu, DL[2]

机构：[1]Gansu Univ Chinese Med, Sci Res & Expt Ctr, Lanzhou 730000, Gansu Province, Peoples R China;[2]Gansu Univ Chinese Med, Sch Pharm, Lanzhou 730000, Gansu Province, Peoples R China;[3]Gansu Univ Chinese Med, Clin Med Coll 1, Lanzhou 730000, Gansu Province, Peoples R China;[4]Gansu Univ Chinese Med, Key Lab Dunhuang Med, Lanzhou 730000, Gansu Province, Peoples R China;[5]Northwest Collaborat Innovat Ctr Tradit Chinese Me, Lanzhou 730000, Gansu Province, Peoples R China;[6]Gansu Pharmaceut Ind Innovat Res Inst, Lanzhou 730000, Gansu Province, Peoples R China;[7]Gansu Univ Chinese Med, Lanzhou 730000, Gansu Province, Peoples R China

第一机构：甘肃中医药大学科研实验中心（甘肃省中医药标准化技术委员会秘书处）

通信机构：[1]corresponding author), Gansu Univ Chinese Med, Sci Res & Expt Ctr, Lanzhou 730000, Gansu Province, Peoples R China;[2]corresponding author), Gansu Univ Chinese Med, Lanzhou 730000, Gansu Province, Peoples R China.|[10735]甘肃中医药大学;[107359c91a78c5fd2e803]甘肃中医药大学科研实验中心（甘肃省中医药标准化技术委员会秘书处）;

年份：2024

卷号：171

外文期刊名：BIOMEDICINE & PHARMACOTHERAPY

收录：;Scopus(收录号：2-s2.0-85184497790);WOS:【SCI-EXPANDED(收录号:WOS:001166744000001)】；

基金：This work was supported by the Innovation Fund Project of Colleges and Universities in Gansu Province (2021 B-160) ; Open Project of Key Laboratory of Dunhuang Medicine, Ministry of Education (DHYX 20-14) ; Project of Scientific Research and Innovation Funding of Gansu University of Chinese Medicine (2020 KCYB-1) . Open Project Funding Guideline of Research Center of Traditional Chinese Medicine, Gansu Province (zyzx-2023-19) .

语种：英文

外文关键词：Alzheimer's disease; Type 2 diabetes; Hypoxia; Hypoxia-inducible factor-1 alpha

摘要：Alzheimer's disease (AD) -related brain deterioration is linked to the type 2 diabetes mellitus (T2DM) features hyperglycemia, hyperinsulinemia, and insulin resistance. Hypoxia as a common risk factor for both AD and T2DM. Hypoxia-inducible factor -1 alpha (HIF-1 alpha) acts as the main regulator of the hypoxia response and may be a key target in the comorbidity of AD and T2DM. HIF-1 alpha expression is closely related to hyperglycemia, insulin resistance, and inflammation. Tissue oxygen consumption disrupts HIF-1 alpha homeostasis, leading to increased reactive oxygen species levels and the inhibition of insulin receptor pathway activity, causing neuroinflammation, insulin resistance, abnormal A beta deposition, and tau hyperphosphorylation. HIF-1 alpha activation also leads to the deposition of A beta by promoting the abnormal shearing of amyloid precursor protein and inhibiting the degradation of A beta, and it promotes tau hyperphosphorylation by activating oxidative stress and the activation of astrocytes, which further exasperates AD. Therefore, we believe that HIF-alpha has great potential as a target for the treatment of AD. Importantly, the intracellular homeostasis of HIF-1 alpha is a more crucial factor than its expression level.