WNK-SPAK/OSR1-NCC kinase signaling pathway as a novel target for the treatment of salt-sensitive hypertension
| العنوان: | WNK-SPAK/OSR1-NCC kinase signaling pathway as a novel target for the treatment of salt-sensitive hypertension |
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| المؤلفون: | Jinwei Zhang, Archie Brown, Zhijuan Wu, Nur Farah Meor Azlan |
| المصدر: | Acta Pharmacol Sin |
| بيانات النشر: | Springer Science and Business Media LLC, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Pseudohypoaldosteronism, Lysine, Secondary hypertension, Blood Pressure, Review Article, Nephron, Protein Serine-Threonine Kinases, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, WNK Lysine-Deficient Protein Kinase 1, medicine, Animals, Humans, Solute Carrier Family 12, Member 3, Pharmacology (medical), Diuretics, Protein Kinase Inhibitors, Thiazide, Adaptor Proteins, Signal Transducing, Pharmacology, urogenital system, Reabsorption, Kinase, Chemistry, Calcium-Binding Proteins, Microfilament Proteins, General Medicine, Cullin Proteins, medicine.disease, Cell biology, 030104 developmental biology, medicine.anatomical_structure, Ion homeostasis, 030220 oncology & carcinogenesis, Oxidative stress, Protein Binding, Signal Transduction, medicine.drug |
| الوصف: | Hypertension is the most prevalent health condition worldwide, affecting ~1 billion people. Gordon’s syndrome is a form of secondary hypertension that can arise due to a number of possible mutations in key genes that encode proteins in a pathway containing the With No Lysine [K] (WNK) and its downstream target kinases, SPS/Ste20-related proline-alanine-rich kinase (SPAK) and oxidative stress responsive kinase 1 (OSR1). This pathway regulates the activity of the thiazide-sensitive sodium chloride cotransporter (NCC), which is responsible for NaCl reabsorption in the distal nephron. Therefore, mutations in genes encoding proteins that regulate the NCC proteins disrupt ion homeostasis and cause hypertension by increasing NaCl reabsorption. Thiazide diuretics are currently the main treatment option for Gordon’s syndrome. However, they have a number of side effects, and chronic usage can lead to compensatory adaptations in the nephron that counteract their action. Therefore, recent research has focused on developing novel inhibitory molecules that inhibit components of the WNK-SPAK/OSR1-NCC pathway, thereby reducing NaCl reabsorption and restoring normal blood pressure. In this review we provide an overview of the currently reported molecular inhibitors of the WNK-SPAK/OSR1-NCC pathway and discuss their potential as treatment options for Gordon’s syndrome. |
| تدمد: | 1745-7254 1671-4083 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::256e0ac98cb551b275a0480140d49328Test https://doi.org/10.1038/s41401-020-0474-7Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....256e0ac98cb551b275a0480140d49328 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17457254 16714083 |
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