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Computational Modeling of Kinase Inhibitors as Anti-Alzheimer Agents

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Computational Modeling of Drugs Against Alzheimer’s Disease

Part of the book series: Neuromethods ((NM,volume 203))

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disease distinguished by memory loss, cognitive dysfunction, impaired functional abilities, and behavioral changes. Being the most common form of senile dementia, AD can be characterized by the presence of two types of neuropathological hallmarks: neurofibrillary tangles (NFTs) and senile plaques (SP). The phosphorylation of tau is controlled and regulated by a group of kinase and phosphatase enzymes, making their systemic balance to be an important issue. Disruption of this equilibrium leads to tau hyperphosphorylation followed by tau aggregation. Inhibition of specific tau kinases, therefore, is a potential strategy to reverse tau pathology. However, new drug discovery comes with its own challenges involving high cost of experimentation, resources, and manpower. Thus, to combat these drawbacks, computational methods like pharmacophore modeling, molecular docking, molecular dynamic (MD) simulation, binding energy analysis, and QSAR are used for screening and prediction of new targets. Besides these, such techniques allow the application of available structural information for generating novel molecules contributing to the rational design of inhibitors. In the present book chapter, we have extensively reviewed different tau kinases, their systemic roles, and mechanism of tau phosphorylation relevant to cause AD. Also, the chapter encompasses different computational studies carried out in the last 4 years on various protein kinases in search of potential anti-Alzheimer’s agents.

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Acknowledgment

PD thanks Indian Council of Medical Research for Research Associateship (File No: BMI/11(35)/2022).

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  1. Drug Theoretics and Cheminformatics Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India

    Priyanka De & Kunal Roy

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  1. Priyanka De
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  1. Department of Pharmaceutical Technology, Jadavpur University, Kolkata, West Bengal, India

    Kunal Roy

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De, P., Roy, K. (2023). Computational Modeling of Kinase Inhibitors as Anti-Alzheimer Agents. In: Roy, K. (eds) Computational Modeling of Drugs Against Alzheimer’s Disease. Neuromethods, vol 203. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3311-3_5

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