In silico and Biological Screening of Phytochemicals against NMDA Receptor for Alzheimer's Disease Therapeutics

Background: Alzheimer's Disease (AD), characterized by irreversible neurodegeneration and cognitive decline, lacks a definitive cure, and current medications merely alleviate symptoms. Cognitive manifestations in AD are linked to disrupted glutamatergic neurotransmission, where beta-Amyloid (A) accumulation at specific synapses interacts with glutamine synthetase, causing enzyme inactivation and subsequent NMDA signalling impairment. Dysregulation of glutamine synthetase leads to NMDA receptor hyper activation, resulting in neuronal damage and cell death. Aim: The focus of this investigation is on N-Methyl D-Aspartate (NMDA) receptors, which belong to the ionotropic glutamate receptor family and play vital roles in various physiological and pathological processes such as neuron development, synaptic plasticity, and central nervous system learning and memory. This study seeks to analyze target data to differentiate between effective and ineffective options for virtual screening. Utilizing this information, the study aims to generate a novel or enhanced reaction product. Materials and Methods: Computational embedding was employed to explore interactions between NMDA receptors and phytoconstituents of selected plants, including Amla, Shankhapushpi, Giloy, Ashwagandha, and Turmeric. ADMET descriptions for well-known botanical compounds were also scrutinized. Results: Structural analysis of 75 compounds derived from selected phytochemicals was conducted based on molecular properties. Key compounds were identified, and additional ADMET properties were evaluated. Quercetin emerged as the top-ranking compound based on shear score, shear strength, and molecular interactions with NMDA receptors. Conclusion: This computational study identifies specific plants as potential NMDA receptor antagonists, offering promise for mitigating Alzheimer's disease symptoms in the future.