ReviewActa pharmacologica Sinica2021
WNK-SPAK/OSR1-NCC kinase signaling pathway as a novel target for the treatment of salt-sensitive hypertension.
Review in Acta pharmacologica Sinica, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 36 citations in OpenAlex.
- Personalized Sequential Nephron Blockade for Diuretic Resistance in Acute Decompensated Heart Failure: A Narrative Review for the Cardiorenal Clinician.Journal of personalized medicine · 2026Review
- Exploring the Role of the SLC12A Cation-Coupled Chloride Cotransporters in the Cardiovascular System.Cells · 2026Review
- From Ion Channels to Blood Pressure: Genetic Disorders of Renal Tubular Transport.Electrolyte & blood pressure : E & BP · 2026Review
- Targeting WNK1 Releases Differentiation Block in Acute Myeloid Leukemia.bioRxiv : the preprint server for biology · 2026Article
- Association of ATP2B1 and STK39 gene variants with blood pressure levels in patients with essential hypertension.Laboratory medicine · 2026Article
- With No-Lysine Kinase 1 Regulates Biotic and Abiotic Stress Tolerance in Rice by Targeting OsCATA to Alter HMolecular plant pathology · 2026Article
- Genetic Variants in the MTHFR and WNK1 Genes and Their Contribution to Hypertension Susceptibility.International journal of medical sciences · 2026Article
- Advances in mechanical force-induced adaptive responses and pathological transition of renal tubular epithelial cells.Frontiers in cell and developmental biology · 2026Review
- Pharmacological inhibition of SPAK-NKCC1 complex attenuates astrogliosis and restores cerebral blood flow in a mouse model of VCID.Acta neuropathologica communications · 2025Article
- WNK1 Alleviates Chloride Efflux-Induced NLRP3 Inflammasome Activation and Subsequent Neuroinflammation in Early Brain Injury Following Subarachnoid Hemorrhage.Neuroscience bulletin · 2025Article
- Genomic Insights into Blood Pressure Regulation: Exploring Ion Channel and Transporter Gene Variations in Jordanian Hypertensive Individuals.Medicina (Kaunas, Lithuania) · 2025Article
- Role of ENaC in gender-associated differences in blood pressure.Iranian journal of basic medical sciences · 2025Article
- Sodium Chloride Cotransporter in Hypertension.Biomedicines · 2024Review
- Structural bases for NaNature communications · 2024Article
- The RELT Family of Proteins: An Increasing Awareness of Their Importance for Cancer, the Immune System, and Development.Biomedicines · 2023Review
- Renal CD81 interacts with sodium potassium 2 chloride cotransporter and sodium chloride cotransporter in rats with lipopolysaccharide-induced preeclampsia.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- Association study ofFrontiers in genetics · 2023Article
- Efficacy of novel SPAK inhibitor ZT-1a derivatives (1c, 1d, 1g & 1h) on improving post-stroke neurological outcome and brain lesion in mice.Neurochemistry international · 2023Article
- Circadian clocks of the kidney: function, mechanism, and regulation.Physiological reviews · 2022Review
- An update regarding the role of WNK kinases in cancer.Cell death & disease · 2022Review
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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