Analogues Rescues Tau Pathologies and Memory Deficits Inhibiting GSK‐3 Signaling using Scaffold morphing and in silico approaches

Abstract

AbstractBackgroundAlzheimer’s disease (AD is caused by plaque agglomeration and entanglement in several areas of the neural cells, which leads to apoptosis. The main etiology of AD is senile dementia, which is linked to amyloid‐beta (Aβ) deregulation and tau perivascular pathogeny. Hyperphosphorylated tau has propensity for microtubules, which elevates the instability and tau‐protein congregates, leading to accumulation of neurofibrillary tangles (NFTs). Tau hyperphosphorylation is susceptible to GSK‐3 and is an emerging hypothesis for AD. As a result, attempts are made to conduct investigations and further advancements on new analogues capable of inhibiting the GSK‐3 protein, which are currently in the clinical trials.MethodIn this analysis, we have evaluated certain GSK‐3 inhibitor variants utilizing scaffolding and framework devise technique with pharmacological characteristics, accompanied by computational screenings (pharmacokinetics and docking).ResultThe structure‐based designed analogues interacted effectively with the active amino acids of GSK‐3β target protein. The in silico pharmacokinetic studies revealed their drug‐like properties.ConclusionThe analogues with best interactions and binding scores will be considered in the future to completely demonstrate their potential relevance as viable GSK ‐ 3 inhibitors.