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SLC13A5作为代谢性疾病潜在药物作用靶点的研究进展

Progress of SLC13A5 as a potential pharmacological target of metabolic diseases

  • 摘要: 溶质载体超家族(solute carrier,SLC)由400多个转运蛋白组成,它们介导离子、核苷酸、糖以及其他外源和内源性物质跨生物膜的流入和流出。现已有研究证实超过80种SLC载体蛋白与人类某些疾病有关,且有超过30种SLC载体蛋白被作为潜在的药物靶点。SLC13A5介导柠檬酸等物质的跨膜转运,后者与脂质从头合成(de novo lipid synthesis,DNL)相关。越来越多的研究发现,SLC13A5与肥胖、胰岛素抵抗和非酒精性脂肪肝病(NAFLD)等代谢性疾病密切相关。目前,针对脂质代谢紊乱引起的代谢性疾病尤其是NAFLD尚无临床治疗特效药。SLC13A5作为一个具有极大开发潜力的靶点,研究其参与代谢性疾病发生、发展过程的分子机制以及进行药物设计与开发意义重大。因此,将SLC13A5对代谢调节的影响以及其作为治疗代谢性疾病潜在靶点的研究进展做一综述,旨在为代谢性疾病相关药物的研究与开发提供必要的参考。

     

    Abstract: The solute carrier (SLC) consists of more than 400 transport proteins mediating the influx and efflux of ions, nucleotides, sugars and other exogenous and endogenous substances across biological membranes. Over 80 SLC carrier proteins have been reported to be closely associated with human diseases, in which more than 30 SLC proteins have been regarded as the potential drug targets. SLC13A5 mediates transmembrane transport of substances such as citrate, which is connected with de novo lipid synthesis (DNL). Studies have found that SLC13A5 is related to metabolic diseases such as obesity, insulin resistance (IR), non-alcoholic fatty liver disease (NAFLD). At present, there is no specific drug for clinical treatment of metabolic diseases caused by lipid metabolism disorders, especially NAFLD. Therefore, this paper summarizes the effect of SLC13A5 on metabolic regulation and its potential as a pharmacological target for metabolic diseases treatment, aiming to provide a reference for the research and development of drugs related to metabolic diseases.

     

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