SK Chand Basha* and Mekala Janaki Ramaiah

Department of Biotechnology, Koneru Lakshmaiah Education Foundation, Vaddeswaram, AP, India

*Corresponding Author: SK Chand Basha, Department of Biotechnology, Koneru Lakshmaiah Education Foundation, Vaddeswaram, AP, India.

Received: August 22, 2024; Published: September 29, 2024

Abstract

Background: Alzheimer’s disease (AD) is a complex and cognitive neurodegenerative disorder effecting millions of people across the globe. Emerging studies suggests that Triggering receptor expressed on myeloid cells 2 (TREM2) associated with late onset Alzheimer’s disease (LOAD). TREM2 are the trans membrane receptors of microglial cells which resides in central nervous system. TREM2 facilitates diverse physiological functions of microglia like phagocytosis. The signalling mechanism of TREM2 is still obscure, pertaining to the same we have proposed a hypothesis in our previous paper. In our hypothesis, we state that the ecto domain of TREM2 exhibit differential binding ability against various forms of Aβ ligands. In the current work we have tested our hypothesis by utilising computational tools. Objective: Two questions arises from our hypothesis that, whether TREM2 has differential binding affinity with Aβ ligands? And To test whether Aβ oligomer has the highest binding affinity with TREM2 ecto domain? The broad objective of our work is to computationally test the TREM2-Aβ ligand binding ability. The current work may pave the way in identification of potential Aβ ligand which have potential therapeutic applications in AD. To corroborate with TREM2 docking studies, we have conducted similar studies on R47H TREM2, which is a mutational variant of TREM2.

Materials and Methods: I-TASSER webserver and AlphaFold data base were utilised for the structural prediction and analysis of TREM2. Totally, 9 different Aβ ligands were utilised for the study. Rigid docking of TREM2 and R47H TREM2 against Aβ ligands were performed by ClusPro and HawkDock servers to signify the differential docking analysis.

Results: Docking results suggests that Aβ 6 and Aβ oligomer ligands were reported as the potential ligands. ClusPro protein-protein interactions suggests that, for both TREM2 and R47H TREM2, Aβ 6 was the potential ligand with cluster size of 337 and 411 respectively. HawkDock results suggests that Aβ oligomer was the potential ligand for both TREM2 and R47H TREM2 exhibiting docking scores of - 4818.30 and - 4142.15 respectively. I-TASSER and AlphaFold servers predicted models of TREM2 structure.

Conclusion: TREM2 structural analysis done by two different web portals explores further insights. Docking studies of TREM2 and R47H TREM2 suggest that Aβ 6 and Aβ oligomer were the potential ligands having therapeutic potential in AD which requires further experimental studies. Finally, our computational examination suggest that, results were in consensus with the first question of hypothesis and in partial consensus with the second question of hypothesis

Keywords: TREM2; R47H TREM2; Aβ Ligands; Alzheimer’s Disease (AD)

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Citation

Citation: SK Chand Basha and Mekala Janaki Ramaiah. “Computational Examination of Microglial TREM2 Structure and its Molecular Docking Analysis against Amyloid-β (Aβ) Ligands with Therapeutic Applications in Alzheimer’s Disease (AD)". Acta Scientific Neurology 7.10 (2024): 21-52.

Copyright

Copyright: © 2024 SK Chand Basha and Mekala Janaki Ramaiah. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.