Kohli Harleen, Kumar Pravir, Ambasta Rashmi K
Molecular Neuroscience and Functional Genomics Laboratory, Delhi Technological University (Formerly Delhi College of Engineering), Delhi 110042, India.
Heliyon. 2021 Feb 12;7(2):e06088. doi: 10.1016/j.heliyon.2021.e06088. eCollection 2021 Feb.
Huntington's disease is a neurodegenerative disease caused by CAG repeat in the first exon of HTT (Huntingtin) gene, leading to abnormal form of Htt protein containing enlarged polyglutamine strands of variable length that stick together to form aggregates and is toxic to brain causing brain damage. Complete reversal of brain damage is not possible till date but recovery may be possible by peptide therapy. The peptide-based therapy for Huntington's disease includes both poly Q peptide as well as non poly Q peptides like (QBP1)2, p42, Exendin 4, ED11, CaM, BiP, Leuprorelin peptide. The novel approach that is currently being tested in this article is the peptide-based therapy to target the mutated protein. This approach is based on the principle of preventing the aggregation of mutant Htt by blocking the potential sites responsible for protein aggregation and thereby ameliorating the disease symptoms. Herein, we have screened a variety of potential peptides that were known to prevent the protein aggregation, comparatively analyzed their binding affinity with homology modeled Htt protein, designed novel peptides based upon conservation analysis among screened potential peptides as a therapeutic agent, comparatively analyzed the therapeutic potential of novel peptides against modeled Htt protein for investigating the therapeutic prospects of Huntington's disease. We have designed a peptide for the therapy of Huntington's disease by comparing several peptides, which are already in use for Huntington's disease.
亨廷顿舞蹈症是一种神经退行性疾病,由HTT(亨廷顿蛋白)基因第一外显子中的CAG重复序列引起,导致Htt蛋白形成异常形式,其中包含长度可变的扩大的聚谷氨酰胺链,这些链聚集在一起形成聚集体,对大脑有毒性,会导致脑损伤。迄今为止,脑损伤无法完全逆转,但通过肽疗法可能实现恢复。用于治疗亨廷顿舞蹈症的肽疗法包括聚Q肽以及非聚Q肽,如(QBP1)2、p42、艾塞那肽4、ED11、钙调蛋白、免疫球蛋白结合蛋白、亮丙瑞林肽。本文目前正在测试的新方法是基于肽的疗法,以靶向突变蛋白。该方法基于通过阻断负责蛋白质聚集的潜在位点来防止突变Htt聚集的原理,从而改善疾病症状。在此,我们筛选了多种已知可防止蛋白质聚集的潜在肽,比较分析了它们与同源建模的Htt蛋白的结合亲和力,基于筛选出的潜在肽之间的保守性分析设计了新型肽作为治疗剂,比较分析了新型肽对建模的Htt蛋白的治疗潜力,以研究亨廷顿舞蹈症的治疗前景。我们通过比较几种已用于治疗亨廷顿舞蹈症的肽,设计了一种用于治疗该疾病的肽。