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溶质载体家族26成员4(SLC26A4),哮喘的一个潜在治疗靶点。

Solute Carrier Family 26 Member 4 (SLC26A4), A Potential Therapeutic Target for Asthma.

作者信息

Guntupalli Vineeta, Wan Rongjun, Liu Liyuan, Gu Wenjing, Xie Shaobing, Gao Peisong

机构信息

Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.

Department of Respiratory and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha 410008, China.

出版信息

J Respir Biol Transl Med. 2024 Jun;1(2). doi: 10.35534/jrbtm.2024.10011. Epub 2024 Jun 25.

Abstract

Asthma is a prevalent respiratory condition with multifaceted pathomechanisms, presenting challenges for therapeutic development. The SLC (Solute Carrier) gene family, encompassing diverse membrane transport proteins, plays pivotal roles in various human diseases by facilitating solute movement across biological membranes. These solutes include ions, sugars, amino acids, neurotransmitters, and drugs. Mutations in these ion channels have been associated with numerous disorders, underscoring the significance of SLC gene families in physiological processes. Among these, the SLC26A4 gene encodes pendrin, an anion exchange protein involved in transmembrane transport of chloride, iodide, and bicarbonate. Mutations in SLC26A4 are associated with Pendred syndrome. Elevated SLC26A4 expression has been linked to airway inflammation, hyperreactivity, and mucus production in asthma. Here, we review novel insights from SLC gene family members into the mechanisms of substrate transport and disease associations, with specific emphasis on SLC26A4. We explore triggers inducing SLC26A4 expression and its contributions to the pathogenesis of pulmonary diseases, particularly asthma. We summarize the inhibitors of SLC26A4 that have shown promise in the treatment of different phenotypes of diseases. While SLC26A4 inhibitors present potential treatments for asthma, further research is imperative to delineate their precise role in asthma pathogenesis and develop efficacious therapeutic strategies targeting this protein.

摘要

哮喘是一种具有多方面发病机制的常见呼吸道疾病,给治疗开发带来了挑战。溶质载体(SLC)基因家族包含多种膜转运蛋白,通过促进溶质跨生物膜移动,在各种人类疾病中发挥关键作用。这些溶质包括离子、糖类、氨基酸、神经递质和药物。这些离子通道的突变与多种疾病相关,突显了SLC基因家族在生理过程中的重要性。其中,SLC26A4基因编码pendrin,一种参与氯离子、碘离子和碳酸氢根跨膜转运的阴离子交换蛋白。SLC26A4的突变与 Pendred 综合征相关。SLC26A4表达升高与哮喘中的气道炎症、高反应性和黏液分泌有关。在此,我们综述了SLC基因家族成员在底物转运机制和疾病关联方面的新见解,特别强调SLC26A4。我们探讨了诱导SLC26A4表达的触发因素及其对肺部疾病,特别是哮喘发病机制的贡献。我们总结了在治疗不同疾病表型方面显示出前景的SLC26A4抑制剂。虽然SLC26A4抑制剂为哮喘提供了潜在的治疗方法,但必须进一步研究以明确它们在哮喘发病机制中的精确作用,并制定针对该蛋白的有效治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/484c/11296660/69775cb8971f/nihms-2004890-f0001.jpg

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