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Recent Advances on the Role of GSK3? in the Pathogenesis of Amyotrophic Lateral Sclerosis.

ABSTRACT: Amyotrophic lateral sclerosis (ALS) is a common neurodegenerative disease characterized by progressive motor neuron degeneration. Although several studies on genes involved in ALS have substantially expanded and improved our understanding of ALS pathogenesis, the exact molecular mechanisms underlying this disease remain poorly understood. Glycogen synthase kinase 3 (GSK3) is a multifunctional serine/threonine-protein kinase that plays a critical role in the regulation of various cellular signaling pathways. Dysregulation of GSK3? activity in neuronal cells has been implicated in the pathogenesis of neurodegenerative diseases. Previous research indicates that GSK3? inactivation plays a neuroprotective role in ALS pathogenesis. GSK3? activity shows an increase in various ALS models and patients. Furthermore, GSK3? inhibition can suppress the defective phenotypes caused by SOD, TDP-43, and FUS expression in various models. This review focuses on the most recent studies related to the therapeutic effect of GSK3? in ALS and provides an overview of how the dysfunction of GSK3? activity contributes to ALS pathogenesis.

SUBMITTER: Choi HJ

PROVIDER: S-EPMC7600609 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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