Pathological role of apoptosis signal-regulating kinase 1 in human diseases and its potential as a therapeutic target for cognitive disorders

Abstract

Cognitive disorders are among the leading causes of health and social issues, as well as socioeconomic burden. Cognitive dysfunction associated with diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, diabetes, and stroke can lead to dementia. Despite extensive efforts, strategies for the prevention and treatment of cognitive dysfunction are scarce. Apoptosis signal-regulating kinase 1 (ASK1) participates in diverse biological pathological processes, such as cell death, survival, and differentiation, and it has been suggested as a therapeutic target in various diseases. However, the role of ASK1 in cognitive dysfunction has not been clearly examined yet. In addition, only a few studies have reported a possible relationship between ASK1 signaling and cognitive deficits. In this review, we summarized experimental evidences regarding the association between ASK1 and the pathogenesis of various diseases. Furthermore, we reviewed preclinical studies supporting the possibility that ASK1 regulation is a promising target for the prevention/treatment of cognitive disorders. Nevertheless, future studies are necessary to investigate the role of ASK1 in the pathogenic mechanisms underlying cognitive dysfunctions, for the translation of preclinical information into clinical application.