HIF-1α 作为AD和T2DM之间的共同链接器
Yang Hai1, Ke Ren2, Yarong Zhang2
1Scientific Research and Experimental Center, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu Province, PR China; Key Laboratory of Dunhuang Medicine, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu Province, PR China.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
|January 19, 2024
概括
缺氧诱导因子-1α (HIF-1α) 在阿尔茨海默病 (AD) 和2型糖尿病 (T2DM) 伴随性疾病中至关重要. 维持HIF-1α稳态,而不仅仅是表达,是治疗AD和T2DM的关键.
科学领域:
- 神经科学是一个神经科学.
- 内分泌学 在内分泌学.
- 细胞生物学 细胞生物学
背景情况:
- 阿尔茨海默病 (AD) 和2型糖尿病 (T2DM) 具有共同的危险因素,如高血糖症,高胰岛素症,胰岛素抵抗和缺氧.
- 缺氧诱导因子-1α (HIF-1α) 是缺氧反应的中心调节者,与AD-T2DM并发症有关.
研究的目的:
- 研究HIF-1α在将T2DM特征与AD进展联系起来的病理机制中的作用.
- 评估HIF-1α作为一种潜在的治疗点,用于管理AD和T2DM的并发症.
主要方法:
- 对文献的审查,将缺氧,HIF-1α,T2DM代谢失调和AD神经病理联系起来.
- 分析受HIF-1α失调影响的分子通路,包括氧化应激,炎症和蛋白质聚合.
主要成果:
- HIF-1α表达与高血糖,胰岛素抵抗和炎症相关,这是T2DM的关键特征.
- 破坏HIF-1α稳态会加剧神经炎症,胰岛素抵抗,粉样β (Aβ) 沉积和TAU高酸化.
- HIF-1α激活通过氧化应激和天体细胞激活促进Aβ沉积和tau病理.
结论:
- HIF-1α在阿尔茨海默氏症的发病过程中发挥着关键作用,特别是在T2DM的背景下.
- 准HIF-1α稳态是一种有前途的治疗策略,用于AD和T2DM的并发症.
- 对于治疗干预,HIF-1α的细胞内稳定比其表达水平更为关键.
相关概念视频
TGF - β Signaling Pathway
7.4K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.4K
Insulin: The Receptor and Signaling Pathways
1.2K
Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but...
1.2K
Regulation of Angiogenesis and Blood Supply
2.6K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.6K
PI3K/mTOR/AKT Signaling Pathway
3.6K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.6K
Intracellular Signaling Affects Focal Adhesions
2.7K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
2.7K
T Cell Activation and Clonal Selection
739
T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
Naive T cells that have not yet encountered an antigen express two primary CD...
739


