Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, India.
Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al Kharj, Saudi Arabia.
CNS Neurosci Ther. 2024 Oct;30(10):e70053. doi: 10.1111/cns.70053.
Huntington's disease (HD) is a devastating neurodegenerative disease that is manifested by a gradual loss of physical, cognitive, and mental abilities. As the disease advances, age has a major impact on the pathogenic signature of mutant huntingtin (mHTT) protein aggregation. This review aims to explore the intricate relationship between aging, mHTT toxicity, and cellular senescence in HD. Scientific data on the interplay between aging, mHTT, and cellular senescence in HD were collected from several academic databases, including PubMed, Google Scholar, Google, and ScienceDirect. The search terms employed were "AGING," "HUNTINGTON'S DISEASE," "MUTANT HUNTINGTIN," and "CELLULAR SENESCENCE." Additionally, to gather information on the molecular mechanisms and potential therapeutic targets, the search was extended to include relevant terms such as "DNA DAMAGE," "OXIDATIVE STRESS," and "AUTOPHAGY." According to research, aging leads to worsening HD pathophysiology through some processes. As a result of the mHTT accumulation, cellular senescence is promoted, which causes DNA damage, oxidative stress, decreased autophagy, and increased inflammatory responses. Pro-inflammatory cytokines and other substances are released by senescent cells, which may worsen the neuronal damage and the course of the disease. It has been shown that treatments directed at these pathways reduce some of the HD symptoms and enhance longevity in experimental animals, pointing to a new possibility of treating the condition. Through their amplification of the harmful effects of mHTT, aging and cellular senescence play crucial roles in the development of HD. Comprehending these interplays creates novel opportunities for therapeutic measures targeted at alleviating cellular aging and enhancing HD patients' quality of life.
亨廷顿病（HD）是一种破坏性的神经退行性疾病，表现为身体、认知和精神能力的逐渐丧失。随着疾病的进展，年龄对突变亨廷顿蛋白（mHTT）聚集的致病特征有重大影响。本综述旨在探讨衰老、mHTT 毒性和 HD 中细胞衰老之间的复杂关系。从包括 PubMed、Google Scholar、Google 和 ScienceDirect 在内的几个学术数据库中收集了有关 HD 中衰老、mHTT 和细胞衰老之间相互作用的科学数据。使用的搜索词是“衰老”、“亨廷顿病”、“突变亨廷顿”和“细胞衰老”。此外，为了收集有关分子机制和潜在治疗靶点的信息，搜索范围扩大到包括“DNA 损伤”、“氧化应激”和“自噬”等相关术语。研究表明，衰老通过一些过程导致 HD 病理生理学恶化。由于 mHTT 的积累，促进了细胞衰老，导致 DNA 损伤、氧化应激、自噬减少和炎症反应增加。衰老细胞释放促炎细胞因子和其他物质，可能加重神经元损伤和疾病进程。针对这些途径的治疗已被证明可以减轻一些 HD 症状并延长实验动物的寿命，为治疗该疾病提供了新的可能性。衰老和细胞衰老通过放大 mHTT 的有害影响，在 HD 的发展中发挥关键作用。理解这些相互作用为针对缓解细胞衰老和提高 HD 患者生活质量的治疗措施创造了新的机会。
