Clinical Laboratory, Shaoxing Seventh People's Hospital (Affiliated Mental Health Center, Medical College of Shaoxing University), Shaoxing, Zhejiang, China; Department of Behavioral Neurosciences, Science Research Center of Medical School, Shaoxing University, Shaoxing, Zhejiang, China.
Department of Behavioral Neurosciences, Science Research Center of Medical School, Shaoxing University, Shaoxing, Zhejiang, China.
Biomed Pharmacother. 2024 Sep;178:117228. doi: 10.1016/j.biopha.2024.117228. Epub 2024 Jul 31.
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid-β outside neurons and Tau protein inside neurons. Various pathological mechanisms are implicated in AD, including brain insulin resistance, neuroinflammation, and endocrinal dysregulation of adrenal corticosteroids. These factors collectively contribute to neuronal damage and destruction. Recently, bile acids (BAs), which are metabolites of cholesterol, have shown neuroprotective potential against AD by targeting the above pathological changes. BAs can enter the systematic circulation and cross the blood-brain barrier, subsequently exerting neuroprotective effects by targeting several endogenous receptors. Additionally, BAs interact with the microbiota-gut-brain (MGB) axis to improve immune and neuroendocrine function during AD episodes. Gut microbes impact BA signaling in the brain through their involvement in BA biotransformation. In this review, we summarize the role and molecular mechanisms of BAs in AD while considering the MGB axis and propose novel strategies for preventing the onset and progression of AD.
阿尔茨海默病（AD）是一种神经退行性疾病，其特征是神经元外的淀粉样β和神经元内的 Tau 蛋白积累。AD 涉及多种病理机制，包括脑胰岛素抵抗、神经炎症和肾上腺皮质激素的内分泌失调。这些因素共同导致神经元损伤和破坏。最近，胆固醇的代谢产物胆汁酸（BAs）通过靶向上述病理变化显示出对 AD 的神经保护潜力。BAs 可以进入体循环并穿过血脑屏障，随后通过靶向几种内源性受体发挥神经保护作用。此外，BAs 与微生物群-肠-脑（MGB）轴相互作用，在 AD 发作期间改善免疫和神经内分泌功能。肠道微生物通过参与 BA 生物转化来影响大脑中的 BA 信号。在这篇综述中，我们总结了 BAs 在 AD 中的作用和分子机制，同时考虑了 MGB 轴，并提出了预防 AD 发作和进展的新策略。
