Role of Presenilin-1 in Modulating Glycogen Synthase Kinase 3 β Expression in the Pathogenesis of Alzheimer’s Disease

This is the authors' abstract. We don't add key points for this paper.

Context: Alzheimer's disease (AD) is a neurodegenerative disorder that is characterized by the presence of neurofibrillary tangles (NFT) and senile plaques caused due to amyloid beta (Aβ) peptide localization in the brain. Evidence Acquisition: Proteolytic cleavage of the amyloid precursor protein (APP) results in the formationof the Aβ plaques via the sequential action of the β -secretase and γsecretase enzyme systems.The function of presenilin -1 (PS-1) as a component of the γsecretase complex, its modulation of the enzyme glycogen synthase kinase 3 beta (GSK3β) and the action of GSK3β in the Wnt/βcatenin canonical pathway has been studied.Subsequently, the ability of the canonical Wnt signaling pathway to activate target genes that prove to be ameliorative in the pathogenesis of Alzheimer's disease has also been demonstrated.The current status of drug products in assuaging the effects of AD have been reported along with the disadvantages associated with their use and alternative therapeutic strategies to counter the same.Results: The PI3K/Akt signaling pathway will untangle the link between PS-1, β -catenin and GSK3β, acting as a phosphorylation "switch" to regulate the downstream effects of its substrates and to provide a module for neuroprotection in AD. Conclusions: The present review intended to unravel the prospective role of presenilin -1 in modulatingGSK3β and to further exploit this link in implicating newer therapeutic interventions.