Department of Exercise and Health Promotion, College of Kinesiology and Health, Chinese Culture University, Taipei 11114, Taiwan.
Division of Neurosurgery, Department of Surgery, Kuang Tien General Hospital, Taichung 43303, Taiwan.
Int J Mol Sci. 2021 Jan 19;22(2):934. doi: 10.3390/ijms22020934.
Proinflammatory response and mitochondrial dysfunction are related to the pathogenesis of neurodegenerative diseases (NDs). Nuclear factor κB (NFκB) activation has been shown to exaggerate proinflammation and mitochondrial dysfunction, which underlies NDs. CDGSH iron-sulfur domain 2 (CISD2) has been shown to be associated with peroxisome proliferator-activated receptor-β (PPAR-β) to compete for NFκB and antagonize the two aforementioned NFκB-provoked pathogeneses. Therefore, CISD2-based strategies hold promise in the treatment of NDs. CISD2 protein belongs to the human NEET protein family and is encoded by the gene (located at 4q24 in humans). In CISD2, the [2Fe-2S] cluster, through coordinates of 3-cysteine-1-histidine on the CDGSH domain, acts as a homeostasis regulator under environmental stress through the transfer of electrons or iron-sulfur clusters. Here, we have summarized the features of CISD2 in genetics and clinics, briefly outlined the role of CISD2 as a key physiological regulator, and presented modalities to increase CISD2 activity, including biomedical engineering or pharmacological management. Strategies to increase CISD2 activity can be beneficial for the prevention of inflammation and mitochondrial dysfunction, and thus, they can be applied in the management of NDs.
促炎反应和线粒体功能障碍与神经退行性疾病（NDs）的发病机制有关。核因子 kappa B（NFκB）的激活被证明会加剧炎症和线粒体功能障碍，这是 NDs 的基础。已经表明 CDGSH 铁-硫结构域 2（CISD2）与过氧化物酶体增殖物激活受体-β（PPAR-β）相关，以竞争 NFκB 并拮抗上述两种 NFκB 引发的发病机制。因此，基于 CISD2 的策略有望用于治疗 NDs。CISD2 蛋白属于人类 NEET 蛋白家族，由 基因（位于人类 4q24 号染色体上）编码。在 CISD2 中，[2Fe-2S]簇通过 CDGSH 结构域上的 3-半胱氨酸-1-组氨酸的坐标，作为环境应激下的内稳态调节剂，通过电子或铁-硫簇的转移起作用。在这里，我们总结了 CISD2 在遗传学和临床方面的特征，简要概述了 CISD2 作为关键生理调节剂的作用，并提出了增加 CISD2 活性的方式，包括生物医学工程或药理学管理。增加 CISD2 活性的策略可有益于预防炎症和线粒体功能障碍，因此可应用于 NDs 的管理。
