Wadan Al-Hassan Soliman, Shaaban Ahmed H, El-Sadek Mohamed Z, Mostafa Salah Abdelfatah, Moshref Ahmed Sherief, El-Hussein Ahmed, Ellakwa Doha El-Sayed, Mehanny Samah S
Department of Oral Biology, Faculty of Dentistry, Galala University, Galala Plateau, Attaka, Suez Governorate, 15888, Egypt.
Department of Biology, Faculty of Science, Galala University, Galala Plateau, Attaka,, Suez Governorate, 15888, Egypt.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Mar 31. doi: 10.1007/s00210-025-04014-0.
Neurodegenerative disorders present significant challenges to modern medicine because of their complex etiology, pathogenesis, and progressive nature, which complicate practical treatment approaches. Mitochondrial dysfunction is an important contributor to the pathophysiology of various neurodegenerative illnesses, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). This review paper examines the current literature highlighting the multifaceted functions of mitochondria, including energy production, calcium signaling, apoptosis regulation, mitochondrial biogenesis, mitochondrial dynamics, axonal transport, endoplasmic reticulum-mitochondrial interactions, mitophagy, mitochondrial proteostasis, and their crucial involvement in neuronal health. The literature emphasizes the increasing recognition of mitochondrial dysfunction as a critical factor in the progression of neurodegenerative disorders, marking a shift from traditional symptom management to innovative mitochondrial-based therapies. By discussing mitochondrial mechanisms, including mitochondrial quality control (MQC) processes and the impact of oxidative stress, this review highlights the need for novel therapeutic strategies to restore mitochondrial function, protect neuronal connections and integrity, and slow disease progression. This comprehensive review aims to provide insights into potential interventions that could transform the treatment landscape for neurodegenerative diseases, addressing symptoms and underlying pathophysiological changes.
神经退行性疾病给现代医学带来了重大挑战,因为它们的病因、发病机制复杂且具有渐进性,这使得实际治疗方法变得复杂。线粒体功能障碍是包括阿尔茨海默病(AD)、帕金森病(PD)和肌萎缩侧索硬化症(ALS)在内的各种神经退行性疾病病理生理学的重要促成因素。这篇综述文章审视了当前的文献,这些文献突出了线粒体的多方面功能,包括能量产生、钙信号传导、细胞凋亡调节、线粒体生物发生、线粒体动力学、轴突运输、内质网 - 线粒体相互作用、线粒体自噬、线粒体蛋白质稳态,以及它们对神经元健康的关键作用。文献强调了越来越多的人认识到线粒体功能障碍是神经退行性疾病进展的关键因素,这标志着从传统的症状管理向基于线粒体的创新疗法的转变。通过讨论线粒体机制,包括线粒体质量控制(MQC)过程和氧化应激的影响,本综述强调了需要新的治疗策略来恢复线粒体功能、保护神经元连接和完整性,并减缓疾病进展。这篇全面的综述旨在深入探讨可能改变神经退行性疾病治疗格局的潜在干预措施,解决症状以及潜在的病理生理变化。