Cytokines and NO-Synthases, Immunity and pathogenesis team, Laboratory of Cellular and Molecular Biology, Faculty of Biological Science, University of sciences and technology Houari Boumediene, Algiers, Algeria.
Artificial intelligence and health team, Laboratory of Cellular and Molecular Biology, Faculty of Biological Science, University of sciences and technology Houari Boumediene, Algiers, Algeria.
J Alzheimers Dis. 2024 Nov;102(1):11-29. doi: 10.1177/13872877241283677. Epub 2024 Oct 3.
Alzheimer's disease (AD) is a neurodegenerative disease with a long preclinical and prodromal stage near 20 years. The neuropathological hallmarks of AD include amyloid plaques, neurofibrillary tangles, and neuroinflammation, those lead to neuronal and synaptic loss. Important fact, oxidative stress participates in the AD development by promoting amyloid-β deposition, tau hyperphosphorylation. However, the inflammatory response and pyroptotic death are mediated by the aberrant expression of NLRP inflammasome activated caspase-1, which leads to cleavage pro-inflammatory cytokines such as pro-interleukin-1β and pro-IL-18. IL-1β, TNF-α, and IL-6 which amplify the neuroinflammation loop, are produce by activated microglia and astrocytes, that can serve as early diagnostic markers or therapeutic targets in AD. In this review, we summarize our current understanding of the role of inflammasome in the pathogenesis of AD, highlighting key issues that need to be addressed to improve the development of new therapies.
阿尔茨海默病（AD）是一种神经退行性疾病，具有近 20 年的长临床前和前驱期。AD 的神经病理学特征包括淀粉样斑块、神经原纤维缠结和神经炎症，这些会导致神经元和突触丢失。重要的是，氧化应激通过促进β淀粉样蛋白沉积、tau 过度磷酸化参与 AD 的发展。然而，炎症反应和细胞焦亡死亡是由异常表达的 NLRP 炎性小体激活的半胱天冬酶-1 介导的，这导致促炎细胞因子如前白细胞介素-1β和前白细胞介素-18 的切割。IL-1β、TNF-α 和 IL-6 放大了神经炎症循环，由激活的小胶质细胞和星形胶质细胞产生，可作为 AD 的早期诊断标志物或治疗靶点。在这篇综述中，我们总结了我们目前对炎性小体在 AD 发病机制中的作用的理解，强调了需要解决的关键问题，以改善新疗法的开发。
