Department of Toxicology, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi 110062, India.
Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India.
Ageing Res Rev. 2023 Sep;90:102022. doi: 10.1016/j.arr.2023.102022. Epub 2023 Jul 23.
Alzheimer's disease (AD) is characterized by an adverse cellular environment and pathological alterations in distinct brain regions. The development is triggered or facilitated by a condition such as hypoxia or ischemia, or inflammation and is associated with disruptions of fundamental cellular functions, including metabolic and ion homeostasis. Increasing evidence suggests that hypoxia may affect many pathological aspects of AD, including oxidative stress, mitochondrial dysfunction, ER stress, amyloidogenic processing of APP, and Aβ accumulation, which may collectively result in neurodegeneration. Further investigation into the relationship between hypoxia and AD may provide an avenue for the effective preservation and pharmacological treatment of this neurodegenerative disease. This review summarizes the effects of normoxia and hypoxia on AD pathogenesis and discusses the underlying mechanisms. Regulation of HIF-1α and the role of its key players, including P53, VEGF, and GLUT1, are also discussed.
阿尔茨海默病（AD）的特征是细胞环境不良和不同脑区的病理性改变。这种发展是由缺氧或缺血等情况引发或促进的，与基本细胞功能的紊乱有关，包括代谢和离子稳态。越来越多的证据表明，缺氧可能影响 AD 的许多病理方面，包括氧化应激、线粒体功能障碍、内质网应激、APP 的淀粉样蛋白生成处理和 Aβ积累，这可能共同导致神经退行性变。进一步研究缺氧与 AD 之间的关系可能为这种神经退行性疾病的有效保护和药物治疗提供途径。这篇综述总结了正常氧和缺氧对 AD 发病机制的影响，并讨论了潜在的机制。还讨论了 HIF-1α的调节及其关键因子（包括 P53、VEGF 和 GLUT1）的作用。
