Atta Avik, Gupta Ayushi, Choudhary Princy, Dwivedi Shrey, Singh Sangeeta
Applied Science Department, Indian Institute of Information Technology, Allahabad, Devghat, Jhalwa, Prayagraj, 211015 Uttar Pradesh India.
3 Biotech. 2023 Nov;13(11):372. doi: 10.1007/s13205-023-03789-4. Epub 2023 Oct 16.
The Central nervous system is blemished by the high incidence of neurodegenerative diseases, which is known to cause disfiguration of regeneration and repair of axonal growth. Recognition of proteins that act as agents of repressing such repair has become the norm to tackle these abominable conditions. One such protein is LINGO1 that act as a repressor for axonal growth. Being one of the critical causative agents of several neurodegenerative pathways. Consequently, its inhibition may tend to help the outcomes of regenerative technologies aiming to outweigh the symptoms of neurodegenerative diseases. For this objective, LINGO1 was targeted with pharmacophore analogs of Fasudil and Ibuprofen, as they are known to have a deterring effect against the concerned protein. 1-Tosyl-2-(chloromethyl)-2,3-dihydro-1H-indole was found showing the least binding score of - 6.8, with verified ADMET admissibility. The pharmacological activity of the said ligand was estimated with QSAR tool showing favourable electro-steric model. All this was finally collaborated with a molecular dynamics simulation study which exhibited a stable structure compatibility of the ligand with LINGO-1. Further, the efficacy of the compound can be evaluated through experimental studies for inferring its future potential and utilization as an effective means to tackle neuronal regeneration and remyleination.
The online version contains supplementary material available at 10.1007/s13205-023-03789-4.
中枢神经系统因神经退行性疾病的高发病率而存在缺陷，已知这些疾病会导致轴突生长的再生和修复出现畸形。识别作为抑制这种修复作用因子的蛋白质已成为应对这些恶劣状况的常态。一种这样的蛋白质是LINGO1，它作为轴突生长的抑制剂。它是几种神经退行性通路的关键致病因素之一。因此，抑制它可能有助于旨在减轻神经退行性疾病症状的再生技术取得更好效果。为了这个目标，用法舒地尔和布洛芬的药效团类似物靶向LINGO1，因为已知它们对相关蛋白质有抑制作用。发现1-对甲苯磺酰基-2-(氯甲基)-2,3-二氢-1H-吲哚的结合分数最低，为-6.8，且具有经验证的药物代谢动力学和毒性性质可接受性。用定量构效关系工具评估了所述配体的药理活性，显示出有利的电子立体模型。所有这些最终与分子动力学模拟研究相结合，该研究展示了配体与LINGO-1的稳定结构相容性。此外，该化合物的功效可通过实验研究进行评估，以推断其未来潜力以及作为解决神经元再生和髓鞘再生的有效手段的用途。
在线版本包含可在10.1007/s13205-023-03789-4获取的补充材料。
