Department of Bioinformatics, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences (SIMATS), Thandalam, Chennai - 602105, Tamil Nadu, India.
Department of Biotechnology, School of Bio Sciences and Technology, Quantitative Biology Lab, Vellore Institute of Technology, Vellore - 632014, Tamil Nadu, India.
Curr Drug Metab. 2022;23(4):260-282. doi: 10.2174/1389200223666220321103942.
Huntington's disease (HD) is a distressing, innate neurodegenerative disease that descends from CAG repeat expansion in the huntingtin gene causing behavioral changes, motor dysfunction, and dementia in children and adults. Mutation in huntingtin (HTT) protein has been suggested to cause neuron loss in the cortex and striatum through various mechanisms, including abnormal regulation of transcription, proteasomal dysfunction, posttranslational modification, and other events regulating toxicity. Pathogenesis of HD involves cleavage of the huntingtin protein followed by the neuronal accumulation of its aggregated form. Several research groups made possible efforts to reduce huntingtin gene expression, protein accumulation, and protein aggregation using inhibitors and molecular chaperones as developing drugs against HD. Herein, we review the mechanism proposed towards the formation of HTT protein aggregation and the impact of therapeutic strategies for the treatment of HD.
亨廷顿病（HD）是一种令人痛苦的、先天性的神经退行性疾病，源于亨廷顿基因中的 CAG 重复扩展，导致儿童和成人出现行为改变、运动功能障碍和痴呆。亨廷顿蛋白（HTT）突变被认为通过多种机制导致皮质和纹状体神经元丢失，包括转录异常调节、蛋白酶体功能障碍、翻译后修饰以及其他调节毒性的事件。HD 的发病机制涉及亨廷顿蛋白的切割，随后其聚集形式在神经元中积累。几个研究小组通过使用抑制剂和分子伴侣来降低亨廷顿基因表达、蛋白积累和蛋白聚集，从而做出了减少 HD 的努力。在此，我们综述了 HTT 蛋白聚集形成的机制以及治疗 HD 的治疗策略的影响。
