Pal Chinmay
Department of Chemistry, Gobardanga Hindu College, North 24 Parganas, West Bengal 743273, India.
Biochim Biophys Acta Mol Basis Dis. 2025 Mar;1871(3):167617. doi: 10.1016/j.bbadis.2024.167617. Epub 2024 Dec 8.
Alzheimer's disease (AD) poses a considerable worldwide health obstacle, marked by gradual cognitive deterioration and neuronal loss. While the molecular mechanisms underlying AD pathology have been elucidated to some extent, therapeutic options remain limited. Mitochondrial dysfunction has become recognized as a significant factor in the development of AD, with oxidative stress and disrupted energy metabolism being critical elements. This review explores the mechanistic aspects of small molecule targeting of mitochondria as a potential therapeutic approach for AD. The review explores the role of mitochondrial dysfunction in AD, including its involvement in the accumulation of β-amyloid plaques and neurofibrillary tangles, synaptic dysfunction, and neuronal death. Furthermore, the effects of oxidative stress on mitochondrial function were investigated, including the resulting damage to mitochondrial components. Mitochondrial-targeted therapies have attracted attention for their potential to restore mitochondrial function and reduce AD pathology. The review outlines the latest preclinical and clinical evidence supporting the effectiveness of small molecules in targeting mitochondrial dysfunction in AD. Additionally, it discusses the molecular pathways involved in mitochondrial dysfunction and examines how small molecules can intervene to address these abnormalities. By providing a comprehensive overview of the latest research in this field, this review aims to shed light on the therapeutic potential of small molecule targeting of mitochondria in AD and stimulate further research in this promising area of drug development.
阿尔茨海默病（AD）是全球范围内一个重大的健康障碍，其特征为认知功能逐渐衰退和神经元丧失。尽管AD病理的分子机制已在一定程度上得到阐明，但治疗选择仍然有限。线粒体功能障碍已被公认为是AD发病的一个重要因素，氧化应激和能量代谢紊乱是其中的关键要素。本综述探讨了小分子靶向线粒体作为AD潜在治疗方法的作用机制。该综述探讨了线粒体功能障碍在AD中的作用，包括其在β-淀粉样蛋白斑块和神经原纤维缠结积累、突触功能障碍及神经元死亡中的作用。此外，还研究了氧化应激对线粒体功能的影响，包括由此导致的线粒体成分损伤。线粒体靶向疗法因其恢复线粒体功能和减轻AD病理的潜力而受到关注。该综述概述了支持小分子靶向AD中线粒体功能障碍有效性的最新临床前和临床证据。此外，还讨论了线粒体功能障碍所涉及的分子途径，并研究了小分子如何进行干预以解决这些异常情况。通过全面概述该领域的最新研究，本综述旨在阐明小分子靶向线粒体在AD中的治疗潜力，并激发在这一有前景的药物研发领域的进一步研究。
