Azam Shofiul, Haque Md Ezazul, Balakrishnan Rengasamy, Kim In-Su, Choi Dong-Kug
Department of Applied Life Sciences, Graduate School, BK21 Program, Konkuk University, Chungju-si, South Korea.
Department of Biotechnology, College of Biomedical and Health Science, Research Institute of Inflammatory Disease (RID), Konkuk University, Chungju-si, South Korea.
Front Cell Dev Biol. 2021 Aug 13;9:683459. doi: 10.3389/fcell.2021.683459. eCollection 2021.
Ageing is an inevitable event in the lifecycle of all organisms, characterized by progressive physiological deterioration and increased vulnerability to death. Ageing has also been described as the primary risk factor of most neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and frontotemporal lobar dementia (FTD). These neurodegenerative diseases occur more prevalently in the aged populations. Few effective treatments have been identified to treat these epidemic neurological crises. Neurodegenerative diseases are associated with enormous socioeconomic and personal costs. Here, the pathogenesis of AD, PD, and other neurodegenerative diseases has been presented, including a summary of their known associations with the biological hallmarks of ageing: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, mitochondrial dysfunction, cellular senescence, deregulated nutrient sensing, stem cell exhaustion, and altered intercellular communications. Understanding the central biological mechanisms that underlie ageing is important for identifying novel therapeutic targets for neurodegenerative diseases. Potential therapeutic strategies, including the use of NAD precursors, mitophagy inducers, and inhibitors of cellular senescence, has also been discussed.
衰老是所有生物体生命周期中不可避免的事件，其特征是生理机能逐渐衰退以及死亡易感性增加。衰老也被描述为大多数神经退行性疾病的主要危险因素，包括阿尔茨海默病（AD）、帕金森病（PD）、亨廷顿病（HD）和额颞叶痴呆（FTD）。这些神经退行性疾病在老年人群中更为普遍。目前几乎没有发现有效的治疗方法来应对这些流行的神经危机。神经退行性疾病会带来巨大的社会经济和个人成本。在此，介绍了AD、PD及其他神经退行性疾病的发病机制，包括它们与衰老生物学标志的已知关联总结：基因组不稳定、端粒磨损、表观遗传改变、蛋白质稳态丧失、线粒体功能障碍、细胞衰老、营养感应失调、干细胞耗竭以及细胞间通讯改变。了解衰老背后的核心生物学机制对于确定神经退行性疾病的新治疗靶点很重要。还讨论了潜在的治疗策略，包括使用NAD前体、线粒体自噬诱导剂和细胞衰老抑制剂。
