Department of Pharmacy, Banasthali Vidyapith, Rajasthan, India.
IIMT College of Pharmacy, IIMT Group of Colleges, Greater Noida, Uttar Pradesh, India.
Ageing Res Rev. 2024 Nov;101:102483. doi: 10.1016/j.arr.2024.102483. Epub 2024 Sep 3.
Alzheimer's Disease (AD), a multifaceted neurodegenerative disorder, is increasingly understood through the regulatory lens of microRNAs (miRNAs). This review comprehensively examines the pivotal roles of miRNAs in AD pathogenesis, shedding light on their influence across various pathways. We delve into the biogenesis and mechanisms of miRNAs, emphasizing their significant roles in brain function and regulation. The review then navigates the complex landscape of AD pathogenesis, identifying key genetic, environmental, and molecular factors, with a focus on hallmark pathological features like amyloid-beta accumulation and tau protein hyperphosphorylation. Central to our discussion is the intricate involvement of miRNAs in these processes, highlighting their altered expression patterns in AD and subsequent functional implications, from amyloid-beta metabolism to tau pathology, neuroinflammation, oxidative stress, and synaptic dysfunction. The predictive analysis of miRNA targets using computational methods, complemented by experimental validations, forms a crucial part of our discourse, unraveling the contributions of specific miRNAs to AD. Moreover, we explore the therapeutic potential of miRNAs as biomarkers and in miRNA-based interventions, while addressing the challenges in translating these findings into clinical practice. This review aims to enhance understanding of miRNAs in AD, offering a foundation for future research directions and novel therapeutic strategies.
阿尔茨海默病（AD）是一种多方面的神经退行性疾病，通过 microRNAs（miRNAs）的调控视角越来越被理解。这篇综述全面考察了 miRNAs 在 AD 发病机制中的关键作用，揭示了它们在各种途径中的影响。我们深入研究了 miRNAs 的生物发生和机制，强调了它们在大脑功能和调节中的重要作用。然后，该综述探讨了 AD 发病机制的复杂景观，确定了关键的遗传、环境和分子因素，重点关注淀粉样蛋白-β积累和 tau 蛋白过度磷酸化等标志性病理特征。miRNAs 在这些过程中的复杂参与是我们讨论的核心，突出了它们在 AD 中的异常表达模式及其随后的功能影响，从淀粉样蛋白-β代谢到 tau 病理学、神经炎症、氧化应激和突触功能障碍。使用计算方法对 miRNA 靶标的预测分析，辅以实验验证，是我们论述的重要组成部分，揭示了特定 miRNAs 对 AD 的贡献。此外，我们探讨了 miRNA 作为生物标志物和 miRNA 为基础的干预措施的治疗潜力，同时解决了将这些发现转化为临床实践的挑战。本综述旨在增强对 AD 中 miRNAs 的理解，为未来的研究方向和新的治疗策略提供基础。
