Advances in the study of the role and molecular mechanism of with‑no‑lysine kinase 3 in nervous system diseases (Review)

Mol Med Rep. 2021 May;23(5):393. doi: 10.3892/mmr.2021.12032. Epub 2021 Mar 24.

Abstract

With‑no‑lysine kinase 3 (WNK3) is a serine/threonine kinase that functions by regulating downstream signaling molecules. WNK3 mainly regulates intracellular and extracellular Na+, Cl‑ and K+ levels by regulating downstream ion transporters, the disruption of which has been associated with cerebral ischemia, epilepsy, glioma and other diseases. In addition, WNK3 was demonstrated to regulate neuronal splicing factor RNA binding fox‑1 homolog‑1 to influence autism. Over the past 20 years, accumulating evidence has reported that dysfunctional WNK3 signaling was involved in the pathologies of various neurological disorders; therefore, WNK3 has become a promising therapeutic target for ameliorating the corresponding symptoms of such disorders. The present review aimed to provide a general overview of the expression patterns and physiological functions of WNK3 signaling and its pathophysiological roles in neurological diseases, such as epilepsy, ischemic brain injury, intracerebral hemorrhage, autism, glioma and schizophrenia.

Keywords: with‑no‑lysine kinase 3; epilepsy; ischemic brain injury; intracerebral hemorrhage; autism; glioma; schizophrenia; neurological disease.

Publication types

  • Review

MeSH terms

  • Brain Injuries / genetics
  • Brain Injuries / pathology
  • Cerebral Hemorrhage / genetics*
  • Cerebral Hemorrhage / pathology
  • Epilepsy / genetics
  • Epilepsy / pathology
  • Humans
  • Ion Transport / genetics*
  • Nervous System Diseases / genetics*
  • Nervous System Diseases / pathology
  • Neurons / metabolism
  • Neurons / pathology
  • Protein Serine-Threonine Kinases / genetics*
  • Signal Transduction / genetics

Substances

  • Protein Serine-Threonine Kinases
  • WNK3 protein, human