Analogues Rescues Tau Pathologies and Memory Deficits Inhibiting GSK‐3 Signaling using Scaffold morphing and in silico approaches
Manjinder Singh, Shuchi Goyal, Divya Thirumal, Pratibha Sharma, Maninder Kaur, Varinder Singh, Thakur Gurjeet Singh- Psychiatry and Mental health
- Cellular and Molecular Neuroscience
- Geriatrics and Gerontology
- Neurology (clinical)
- Developmental Neuroscience
- Health Policy
- Epidemiology
Abstract
Background
Alzheimer’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.
Method
In 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).
Result
The 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.
Conclusion
The analogues with best interactions and binding scores will be considered in the future to completely demonstrate their potential relevance as viable GSK ‐ 3 inhibitors.