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靶向蛋白受体和酶精准管理尿石症:全面综述。

Targeting protein receptors and enzymes for precision management of urolithiasis: A comprehensive review.

机构信息

Anjumane-I-Islam Kalsekar Technical Campus (AIKTC), School of Pharmacy, Plot No: 2&3, Sector:16, Near Thana Naka, Khandagaon, New Panvel, Mumbai, Maharashtra 410206, India; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Maulana Azad University, Village Bujhawar, Tehsil Luni, Jodhpur, Rajasthan, 342802, India.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Maulana Azad University, Village Bujhawar, Tehsil Luni, Jodhpur, Rajasthan, 342802, India.

出版信息

Eur J Pharmacol. 2024 Oct 15;981:176904. doi: 10.1016/j.ejphar.2024.176904. Epub 2024 Aug 15.

Abstract

Urolithiasis, characterized by the formation of solid crystalline structures within the urinary tract, presents a significant global health burden with high recurrence rates and limited treatment efficacy. Recent research has identified various protein receptors and enzymes implicated in the pathogenesis of urolithiasis, offering potential targets for therapeutic intervention. Protein receptors such as the calcium-sensing receptor and vasopressin V2 receptor play crucial roles in regulating urinary calcium excretion and water reabsorption, respectively, influencing stone formation. Additionally, modulation of receptors like the angiotensin II receptor and aldosterone receptor can impact renal function and electrolyte balance, contributing to stone prevention. Furthermore, enzymes such as urease inhibitors and xanthine oxidase inhibitors offer targeted approaches to prevent the formation of specific stone types. This review discusses the potential of targeting these receptors and enzymes for the treatment of urolithiasis, exploring associated drugs and their mechanisms of action. Despite promising avenues for personalized and precision medicine approaches, challenges such as the need for robust clinical evidence and ensuring cost-effectiveness must be addressed for the translation of these interventions into clinical practice. By overcoming these challenges, receptor-targeted therapies and enzyme inhibitors hold promise for revolutionizing the management of urolithiasis and reducing its global burden.

摘要

尿路结石病的特征是在尿路中形成固体结晶结构,具有较高的复发率和有限的治疗效果,因此成为全球健康的重大负担。最近的研究已经确定了各种参与尿路结石病发病机制的蛋白受体和酶,为治疗干预提供了潜在的靶点。钙敏感受体和血管加压素 V2 受体等蛋白受体分别在调节尿钙排泄和水重吸收方面发挥着关键作用,影响结石的形成。此外,调节血管紧张素 II 受体和醛固酮受体等受体可以影响肾功能和电解质平衡,有助于预防结石。此外,乌洛托品酶抑制剂和黄嘌呤氧化酶抑制剂等酶类提供了针对特定结石类型形成的靶向治疗方法。本文讨论了针对这些受体和酶治疗尿路结石病的潜力,探讨了相关药物及其作用机制。尽管针对个体化和精准医学方法的途径很有前景,但仍需要解决需要强有力的临床证据和确保成本效益等挑战,才能将这些干预措施转化为临床实践。通过克服这些挑战,受体靶向治疗和酶抑制剂有望彻底改变尿路结石病的管理方式,降低其全球负担。

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