溶质载体家族 26 成员 4 (SLC26A4)--哮喘的潜在治疗靶点

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

哮喘是一种常见的呼吸系统疾病,具有多方面的病理机制,给治疗方法的开发带来了挑战。SLC(溶质载体)基因家族包括多种膜转运蛋白,通过促进溶质在生物膜上的移动,在各种人类疾病中发挥着关键作用。这些溶质包括离子、糖、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,凸显了 SLC 基因家族在生理过程中的重要性。其中,SLC26A4 基因编码一种参与氯化物、碘化物和碳酸氢盐跨膜转运的阴离子交换蛋白--pendrin。SLC26A4 基因突变与彭德综合征有关。SLC26A4 表达的升高与哮喘患者的气道炎症、高反应性和粘液分泌有关。在此,我们回顾了 SLC 基因家族成员对底物转运和疾病相关机制的新见解,并特别强调了 SLC26A4。我们探讨了诱导 SLC26A4 表达的诱因及其对肺部疾病(尤其是哮喘)发病机制的贡献。我们总结了有望治疗不同表型疾病的 SLC26A4 抑制剂。虽然 SLC26A4 抑制剂具有治疗哮喘的潜力,但进一步的研究仍势在必行,以确定其在哮喘发病机制中的确切作用,并开发出针对该蛋白的有效治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Solute Carrier Family 26 Member 4 (SLC26A4), A Potential Therapeutic Target for Asthma.

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.

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