Department of Biotechnology, University of Central Punjab Lahore, Lahore, Pakistan.
Biogerontology. 2024 Oct 29;26(1):5. doi: 10.1007/s10522-024-10147-1.
The iron-sulfur domain (CISD) proteins of CDGSH are classified into three classes: CISD1, CISD2, and CISD3. During premature ageing, mutations that affect these proteins, namely their binding sites, could result in reduced protein production and an inability to preserve cellular integrity. Consequently, this leads to the development of conditions such as diabetes. Notably, CISD3 plays a crucial role in the management of age-related disorders such as Wolfram syndrome, which is often referred to as DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness). Computational analyses have predicted that CISD3 regulates the redox state, safeguards the endoplasmic reticulum and mitochondria, and maintains intracellular calcium levels. CISD3, a member of a recently discovered gene family associated with the CDGSH iron protein apoptotic compensatory response, fulfils a crucial function in mitigating the effects of accelerated ageing. The compound "(-)-(2S)-7,4'-Dihydroxyflavanone" has been discovered by computational drug design as a possible activator of CISD3. It shows potential therapeutic benefits in ameliorating metabolic dysfunction and enhancing glucose regulation. The ligand binds to the binding pocket of the CISD3 protein, increasing the stability of the protein and enhancing its functionality. The current research investigates the binding processes of the molecule in various structures and its anticipated effects on these tissues, therefore providing valuable insights into the mitigation of age-related diabetes and metabolic dysfunction. The projected tripling of the worldwide population of individuals aged 50 and above by 2050 necessitates the urgent development of immunoinformatics-based approaches, including pharmaceutical therapies that target CISD3, to prevent age-related pathologies. The stimulation of CISD3, namely by compounds such as "(-)-(2S)-7,4'-Dihydroxyflavanone", has the potential to counteract telomere shortening and improve metabolic pathways.
铁硫结构域（CISD）蛋白的 CDGSH 被分为三类：CISD1、CISD2 和 CISD3。在衰老过程中，影响这些蛋白质的突变，即它们的结合位点，可能导致蛋白质产量减少和无法维持细胞完整性。因此，这会导致糖尿病等疾病的发展。值得注意的是，CISD3 在管理与年龄相关的疾病方面发挥着关键作用，例如常被称为 DIDMOAD（尿崩症、糖尿病、视神经萎缩和耳聋）的 Wolfram 综合征。计算分析预测 CISD3 调节氧化还原状态、保护内质网和线粒体，并维持细胞内钙水平。CISD3 是一个与 CDGSH 铁蛋白凋亡补偿反应相关的新发现基因家族的成员，在减轻加速衰老的影响方面发挥着关键作用。通过计算药物设计发现的化合物“(-)-(2S)-7,4'-二羟基黄烷酮”可能是 CISD3 的激活剂。它在改善代谢功能和增强葡萄糖调节方面显示出潜在的治疗益处。该配体与 CISD3 蛋白的结合口袋结合，增加了蛋白质的稳定性并增强了其功能。目前的研究调查了分子在各种结构中的结合过程及其对这些组织的预期影响，从而为减轻与年龄相关的糖尿病和代谢功能障碍提供了有价值的见解。预计到 2050 年，全球 50 岁及以上人口将增加两倍，因此迫切需要开发基于免疫信息学的方法，包括针对 CISD3 的药物治疗，以预防与年龄相关的疾病。刺激 CISD3，例如通过“(-)-(2S)-7,4'-二羟基黄烷酮”等化合物，可以抵消端粒缩短并改善代谢途径。
