Published May 1, 2020 | Version v1
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Research Progress of Spironolactone as an Antagonist of NRG1-ERBB4 Pathway in the Treatment of Cognitive Impairment in Schizophrenia

Creators

  • 1. Xi'an Medical University, Xi'an, Shaanxi, 710021, China
  • 2. Xi'an Mental Health Center, Xi'an, Shaanxi, 710061, China

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Abstract

Cognitive dysfunction is one of the core symptoms of schizophrenic patients. The prognosis of patients’ cognitive function is closely related to the overall social function. The use of antipsychotic drugs to improve the cognitive impairment of schizophrenic patients is not yet ideal. The NRG1-ERBB4 signaling pathway acts on the prefrontal cortex. Abnormality of this pathway can affect cognitive function. Currently, spironolactone as an antagonist of nrg1-erbb4 signaling pathway, it is used in the clinical treatment of patients with schizophrenia. This article reviews spironolactone as an NRG1-ERBB4 signaling pathway antagonist that significantly improves cognitive dysfunction in patients with schizophrenia., and further provides theoretical and clinical basis for clinical treatment of cognitive dysfunction.

Schizophrenia is a severe crippled chronic mental illness characterized by positive symptoms (hallucinations and delusions), negative symptoms (social withdrawal) and cognitive impairment (executive function and memory impairment) [1,2]. According to a study by Yueqin Huang et al. [3] in 2019, the lifetime prevalence rate of schizophrenia spectrum disorder in China is 0.7%. Among them, cognitive dysfunction is one of the core symptoms of schizophrenia, the cognitive function of patients is closely related to the outcome of their overall social function. Cognitive impairment is very common in patients with schizophrenia, many areas have been impaired, including language, attention, processing speed, working memory, visual memory, executive function and social cognition [4,5]. Due to the unknown pathogenesis of schizophrenia spectrum disorder and the lack of specific biomarkers, although antipsychotics can improve the positive symptoms of patients, they have little effect on negative symptoms and cognitive impairment [6-8]. The improvement of cognitive dysfunction has a far-reaching impact on the treatment of schizophrenia, but due to professional knowledge, resources and time constraints, we seldom evaluate it in clinical practice, and the therapeutic effect of antipsychotics is not obvious. Therefore, it is necessary to develop and explore more targeted therapies for cognitive disorders in schizophrenia. Some related studies have shown that the NRG1/ ERBB4 signaling pathway has the potential to become a new therapeutic target for the treatment of schizophrenia. Screening among drugs approved by NIH-NCC, spironolactone, a glucocorticoid receptor antagonist, was found to be an inhibitor of ERBB4 activity and reduced the level of ERBB4 phosphorylation in human xenogeneic T-47D cells and Nrg1 transgenic mice in vitro. Nrg1 transgenic schizophrenic mice treated with spironolactone showed positive symptoms and improved working memory function [9]. This article expounds the related studies on spironolactone in the treatment of cognitive impairment of schizophrenia in recent years, in order to provide further reference for the treatment of cognitive impairment of schizophrenia.

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International Journal of Clinical and Medical Cases (ISSN:2517-7346)

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