Kunwar Omkar Kumar, Singh Shamsher
Neuropharmacology Division, Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab, 142001, India.
Neurogenetics. 2025 Jan 17;26(1):21. doi: 10.1007/s10048-025-00801-2.
Huntington's disease (HDs) is a fatal, autosomal dominant, and hereditary neurodegenerative disorder characterized by progressive motor dysfunction, cognitive decline, and psychiatric disturbances. HD is well linked to mutation in the HTT gene, which leads to an abnormal expansion of trinucleotide CAG repeats, resulting in the production of the mHTT protein and responsible for abnormally long poly-Q tract. These abnormal proteins disrupt cellular processes, including neuroinflammation, endoplasmic reticulum (ER) stress, and mitochondrial dysfunction, ultimately leading to selective neuronal loss in the brain. Epidemiological studies reveal significant regional variability in HDs prevalence, with the highest rates observed in North America and the lowest in Africa. In addition to genetic factors, environmental influences such as exposure to metals, and chemicals, and lifestyle factors like alcohol and tobacco use may exacerbate disease progression. This review explores the molecular mechanisms underlying HDs and emphasize the role of neuroinflammatory mediators and environmental factors, in HD research. Understanding these complex interactions is crucial for developing targeted interventions that can slow or halt the progression of this devastating disease.
亨廷顿舞蹈症（HDs）是一种致命的常染色体显性遗传性神经退行性疾病，其特征为进行性运动功能障碍、认知衰退和精神障碍。HD与HTT基因突变密切相关，该突变导致三核苷酸CAG重复序列异常扩增，产生突变型亨廷顿蛋白（mHTT）并形成异常长的多聚谷氨酰胺链。这些异常蛋白质扰乱细胞进程，包括神经炎症、内质网应激和线粒体功能障碍，最终导致大脑中神经元选择性丢失。流行病学研究显示，HDs患病率存在显著的地区差异，北美地区患病率最高，非洲地区最低。除遗传因素外，接触金属和化学物质等环境影响以及饮酒和吸烟等生活方式因素可能会加剧疾病进展。本综述探讨了HDs的分子机制，并强调了神经炎症介质和环境因素在HD研究中的作用。了解这些复杂的相互作用对于开发能够减缓或阻止这种毁灭性疾病进展的靶向干预措施至关重要。
