Akt signaling pathway: a potential therapy for Alzheimer’s disease through glycogen synthase kinase 3 beta inhibition

Abstract

Abstract Alzheimer’s disease (AD) is a form of dementia marked by the accumulation of neuritic plaques and neurofibrillary tangles through the action of GSK-3β with both significant epidemiological and clinical impact. Current pharmacological treatment approaches are focused on symptomatic relief and aims to suppress AD’s progression rather than disease modification. This issue has triggered further investigations about tau pathology as an important component in AD’s pathophysiology, one of them being the Akt signaling pathway. Based on the problem served by AD, combined with the non-existence of conclusive therapy for this disease; hence, this study strives to further investigate the potential therapeutical benefit of Akt signaling towards AD. A total of 82 studies are included, consisting of both national and international articles creating a narrative review based on the PRISMA checklist. Variables searched on this study, include Alzheimer’s disease (AD), Akt signaling, serine-9 phosphorylation, and GSK-3β. Tau protein accumulation has been a mainstay in the physiopathology of AD, which are largely influenced by the GSK-3β expression. Akt signaling has been shown to inactivate GSK-3β through serine-9 phosphorylation. Thus, modulating and optimizing the Akt signaling pathway present encouraging prospects for the development of innovative and efficacious therapeutic strategies in addressing AD. Several studies have tried to estimate the harm and benefit as well as dose–effect relationship between Akt signaling and AD, concluding a promising beneficial effect for AD therapy. Here, we show the beneficial therapeutic effects of Akt signaling towards AD through both theoretical and empirical standpoints.

Keywords

• Alzheimer disease (AD)
• Glycogen synthase kinase-3 beta (GSK-3β) protein
• Phosphorylation
• Physiopathology
• Protein kinase B