Author(s): Kye Vern Kee, Yi Suan Lim, Ee Xion Tan, Wai Keat Yam

Email(s): vernisekkv98@gmail.com , yisuanlim@gmail.com , eexiontan@imu.edu.my , waikeatyam@imu.edu.my

DOI: 10.52711/0974-360X.2025.00011   

Address: Kye Vern Kee1, Yi Suan Lim2, Ee Xion Tan3, Wai Keat Yam4
1IMU University 126, Jalan Jalil Perkasa 19, Bukit Jalil, 57000 Kuala Lumpur, Malaysia.
2School of Data Sciences, Perdana University, Kuala Lumpur, Malaysia.
3IMU University 126, Jalan Jalil Perkasa 19, Bukit Jalil, 57000 Kuala Lumpur, Malaysia.
4IMU University 126, Jalan Jalil Perkasa 19, Bukit Jalil, 57000 Kuala Lumpur, Malaysia.
*Corresponding Author

Published In:   Volume - 18,      Issue - 1,     Year - 2025


ABSTRACT:
Alzheimer disease (AD) is a progressive degenerative disorder of the brain resulting in the loss of higher cognitive function and is considered as the most common form of dementia. It is characterised by a triad of pathological changes in the brain and there have been many proposed approaches and research aimed at treating AD. The two hallmark substrates causing the cognitive decline in AD are the amyloid beta (Aß) plaques deposition, and the neurofibrillary tangles of hyperphosphorylated (HP) tau. In recent years, the focus on research has been based on the Aß hypothesis. However, the failed clinical drug trials targeting Aß suggest that tau related therapies may be a more viable approach to AD treatment. The purpose of this study aims to discover hyperphosphorylated tau protein inhibitor by repurposing the available drugs on the market and subsequently, study its potentials using various molecular modelling methods. The work started with homology modelling on its conserved region, followed by virtual screening of repurposed drugs that could pass through the blood brain barrier. Subsequently, molecular docking was performed on the hyperphosphorylated tau model, and the potential inhibitors identified from the virtual screening. Molecular dynamics simulation was performed to further optimise hyperphosphorylated tau model and top 2 ranked compounds from docking studies. The findings from this study suggested that a potential repurposed drug list that could be potential compounds in inhibiting the aggregation of HP tau protein and can be further explored being a potential treatment for AD.


Cite this article:
Kye Vern Kee, Yi Suan Lim, Ee Xion Tan, Wai Keat Yam. Repurposing Drugs for Inhibition of Hyperphosphorylated Tau Protein in Alzheimer’s Disease: Molecular Modelling Studies. Research Journal of Pharmacy and Technology. 2025;18(1):67-5. doi: 10.52711/0974-360X.2025.00011

Cite(Electronic):
Kye Vern Kee, Yi Suan Lim, Ee Xion Tan, Wai Keat Yam. Repurposing Drugs for Inhibition of Hyperphosphorylated Tau Protein in Alzheimer’s Disease: Molecular Modelling Studies. Research Journal of Pharmacy and Technology. 2025;18(1):67-5. doi: 10.52711/0974-360X.2025.00011   Available on: https://rjptonline.org/AbstractView.aspx?PID=2025-18-1-11


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