Role of Glycogen Synthase Kinase 3 in Molecular Pathology of Alzheimer’s Disease

Abstract

Background: Glycogen synthase kinase 3 (GSK-3) is the evolutionary well-preserved multifunctional ubiquitously expressed kinase. In brain, GSK-3 mediates its effects via cascade of intra-cellular signalling pathways that regulate several functions including memory, behaviour, synapse plasticity, bioenergetics, and neuronal fate determination. Several evidences on transgenic mice models and reports from the post-mortem of AD brains posit that altered levels of GSK-3 are closely linked with several pathological features including impaired splitting of amyloid precursor protein, hyperphosphorylation of Tau, mitochondrial dysfunctions, impaired energetics, maladaptive plasticity of neuronal circuitries in dementia, culminating into pathology of Alzheimer’s disease along with other neurodegenerative diseases. Aim & Objective: Present paper has an aim to analyse the role of GSK3b in molecular pathology of Alzheimer’s disease. The involvement of dysregulated GSK3b in the pathophysiology of Alzheimer’s disease is discussed in the critical review paper covering several factors that either contribute to GSK3b dysregulation or interact with dysregulated GSK3b in the pathogenesis of AD. Research Methodology: Critical analytic, qualitative cum retrospective research study design is adopted utilizing secondary data from books, monographs, journals, conference proceedings for the critical evaluation leading to conclusions beneficial either in future research study or in understanding intricate molecular events for pharmaceutical intervention either to ameliorate the clinical manifestations of Alzheimer’s disease or to delays the progression of disease for the benefit of patients with AD. Findings/Result: Several stressors induce overexpression/aberrant activity of GSK3b leading to increased Amyloid beta formation, tau phosphorylation, mitochondrial dysfunction, impaired synaptic activity, release of pro-inflammatory cytokines and other manifestations implicated in the molecular pathology of Alzheimer’s disease. Originality of Paper: Comprehensive approach was adopted to include papers related to the topic within frame-work of inclusion and exclusion criteria to deduce conclusion. Paper Type: Critical analytic review paper.