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miRNAs 在调节线粒体动态、淀粉样β纤维形成、小胶质细胞激活和胆碱能信号转导中的调控作用:对阿尔茨海默病发病机制的影响。

Regulatory roles of microRNAs in modulating mitochondrial dynamics, amyloid beta fibrillation, microglial activation, and cholinergic signaling: Implications for alzheimer's disease pathogenesis.

机构信息

Department of Pharmacology, Faculty of Pharmacy, Swami Vivekanand Subharti University, Meerut, Uttar Pradesh, India.

Department of Pharmacy, Meerut Institute of Engineering and Technology, Meerut, Uttar Pradesh, India.

出版信息

Neurosci Biobehav Rev. 2024 Jun;161:105685. doi: 10.1016/j.neubiorev.2024.105685. Epub 2024 Apr 25.

DOI:10.1016/j.neubiorev.2024.105685
PMID:38670299
Abstract

Alzheimer's Disease (AD) remains a formidable challenge due to its complex pathology, notably involving mitochondrial dysfunction and dysregulated microRNA (miRNA) signaling. This study delves into the underexplored realm of miRNAs' impact on mitochondrial dynamics and their interplay with amyloid-beta (Aβ) aggregation and tau pathology in AD. Addressing identified gaps, our research utilizes advanced molecular techniques and AD models, alongside patient miRNA profiles, to uncover miRNAs pivotal in mitochondrial regulation. We illuminate novel miRNAs influencing mitochondrial dynamics, Aβ, and tau, offering insights into their mechanistic roles in AD progression. Our findings not only enhance understanding of AD's molecular underpinnings but also spotlight miRNAs as promising therapeutic targets. By elucidating miRNAs' roles in mitochondrial dysfunction and their interactions with hallmark AD pathologies, our work proposes innovative strategies for AD therapy, aiming to mitigate disease progression through targeted miRNA modulation. This contribution marks a significant step toward novel AD treatments, emphasizing the potential of miRNAs in addressing this complex disease.

摘要

阿尔茨海默病(AD)仍然是一个巨大的挑战,因为其病理复杂,特别是涉及线粒体功能障碍和 miRNA 信号失调。本研究深入探讨了 miRNA 对线粒体动力学的影响及其与 AD 中淀粉样蛋白-β(Aβ)聚集和 tau 病理学的相互作用这一尚未充分研究的领域。针对已确定的空白,我们的研究利用先进的分子技术和 AD 模型,以及患者的 miRNA 谱,来揭示在调节线粒体方面起关键作用的 miRNA。我们阐明了影响线粒体动力学、Aβ 和 tau 的新 miRNA,深入了解了它们在 AD 进展中的机制作用。我们的发现不仅增强了对 AD 分子基础的理解,还强调了 miRNA 作为有前途的治疗靶点的潜力。通过阐明 miRNA 在线粒体功能障碍中的作用及其与 AD 标志性病理学的相互作用,我们的工作为 AD 治疗提出了创新策略,旨在通过靶向 miRNA 调节来减轻疾病进展。这项工作是朝着新的 AD 治疗方法迈出的重要一步,强调了 miRNA 在解决这种复杂疾病方面的潜力。

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