Singh Shreya, Singh Rakesh Kumar
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Raebareli Transit Campus, Bijnour-Sisendi Road, Sarojini Nagar, Lucknow, Uttar Pradesh, 226002, India.
Mol Biol Rep. 2025 Jan 29;52(1):173. doi: 10.1007/s11033-025-10297-6.
Alzheimer's disease (AD) is a common neurodegenerative disease characterized by progressive memory loss and cognitive decline. The processes underlying the pathophysiology of AD are still not fully understood despite a great deal of research. Since mitochondrial dysfunction affects cellular energy metabolism, oxidative stress, and neuronal survival, it is becoming increasingly clear that it plays a major role in the development of AD. This review summarizes the recent developments of mitochondrial dysfunction in AD, emphasizing mitochondrial biogenesis, dynamics, axonal transport, interactions between endoplasmic reticulum and mitochondria, mitophagy, and mitochondrial proteostasis. It emphasizes how tau and amyloid-beta (Aβ) proteins worsen mitochondrial and synaptic dysfunction by impairing adenosine triphosphate (ATP) synthesis, causing oxidative stress, and upsetting equilibrium. Additionally, important processes controlling mitochondrial activity and their correlation to the brain health are also discussed. One of the promising therapeutic approaches to lessen neurodegeneration and cognitive decline in AD is to improve mitochondrial activity. This study highlights possible directions for creating focused therapies to impede the advancement of AD through incorporating knowledge of mitochondrial biogenesis and its related mechanisms.
阿尔茨海默病（AD）是一种常见的神经退行性疾病，其特征为进行性记忆丧失和认知衰退。尽管进行了大量研究，但AD病理生理学背后的过程仍未完全明了。由于线粒体功能障碍会影响细胞能量代谢、氧化应激和神经元存活，越来越清楚的是，它在AD的发展中起主要作用。本综述总结了AD中线粒体功能障碍的最新进展，重点关注线粒体生物发生、动力学、轴突运输、内质网与线粒体之间的相互作用、线粒体自噬以及线粒体蛋白质稳态。它强调了tau蛋白和β-淀粉样蛋白（Aβ）如何通过损害三磷酸腺苷（ATP）合成、引起氧化应激和破坏平衡来加剧线粒体和突触功能障碍。此外，还讨论了控制线粒体活性的重要过程及其与大脑健康的相关性。改善线粒体活性是减轻AD神经退行性变和认知衰退的一种有前景的治疗方法。本研究通过纳入线粒体生物发生及其相关机制的知识，突出了创建针对性疗法以阻止AD进展的可能方向。
