Geldenhuys Werner J, Leeper Thomas C, Carroll Richard T
Department of Pharmaceutical Sciences, College of Pharmacy, Northeast Ohio Medical University, Rootstown, OH 44272, USA.
Department of Chemistry, University of Akron, Akron, OH, USA.
Drug Discov Today. 2014 Oct;19(10):1601-6. doi: 10.1016/j.drudis.2014.05.001. Epub 2014 May 9.
Mitochondrial dysfunction plays an important part in the pathology of several diseases, including Alzheimer's disease and Parkinson's disease. Targeting mitochondrial proteins shows promise in treating and attenuating the neurodegeneration seen in these diseases, especially considering their complex and pleiotropic origins. Recently, the mitochondrial protein mitoNEET [also referred to as CDGSH iron sulfur domain 1 (CISD1)] has emerged as the mitochondrial target of thiazolidinedione drugs such as the antidiabetic pioglitazone. In this review, we evaluate the current understanding regarding how mitoNEET regulates cellular bioenergetics as well as the structural requirements for drug compound association with mitoNEET. With a clear understanding of mitoNEET function, it might be possible to develop therapeutic agents useful in several different diseases including neurodegeneration, breast cancer, diabetes and inflammation.
线粒体功能障碍在包括阿尔茨海默病和帕金森病在内的多种疾病的病理过程中起着重要作用。针对线粒体蛋白在治疗和减轻这些疾病中出现的神经退行性变方面显示出前景，特别是考虑到它们复杂且多效性的起源。最近，线粒体蛋白米托内特（也称为CDGSH铁硫结构域1，即CISD1）已成为噻唑烷二酮类药物（如抗糖尿病药物吡格列酮）的线粒体靶点。在本综述中，我们评估了目前对米托内特如何调节细胞生物能学的理解以及药物化合物与米托内特结合的结构要求。清楚了解米托内特的功能后，有可能开发出对包括神经退行性变、乳腺癌、糖尿病和炎症在内的几种不同疾病有用的治疗药物。
