What is it about?
In this study, the interactions between tau fibrils, a protein associated with Alzheimer's disease, and different types of lipids are investigated using computer models. By analyzing the structure of the protein and performing molecular docking and dynamics simulations, the study reveals the amphipathic nature of tau-PHF and highlights the potential energy levels and H-bonding interactions between the protein and specific lipids. These findings could inform future research on Alzheimer's disease and potential therapies.
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Why is it important?
This study is significant because it examines the role of the tau protein in Alzheimer's disease, which has become increasingly important as β-amyloid therapies have failed in clinical trials. Using the structure of paired helical tau filaments (tau-PHF) obtained from the brain of AD, the study examines the interactions between tau-PHF and three lipids: 3-alpha-cholesterol, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, and C18:1 sphingomyelin. Molecular docking, molecular dynamics and analyzes of the natural binding orbitals allowed the researchers to investigate the binding affinity of the lipids to tau-PHF. The study found that tau-PHF has an amphipathic nature, meaning that it has both hydrophobic and hydrophilic regions that can interact with different types of molecules. The researchers also found that the embedded phosphocholine on the tail side of the lipids has high potential energy values and forms hydrogen bonds with some amino acids of tau-PHF. These findings are significant because they shed light on the potential of the tau protein as a strategy for treating Alzheimer's disease. By understanding the interactions between the tau protein and lipids, researchers can develop new compounds that can bind to the tau protein and modulate its function. Ultimately, this study contributes to ongoing efforts to develop new therapies for Alzheimer's disease that target different proteins and signaling pathways than those that have failed in previous clinical trials.
Perspectives
This research advances our understanding of Alzheimer's disease and the role of tau in its pathology. The failure of β-amyloid therapies has prompted researchers to explore new avenues, and this study demonstrates the potential of computational modeling to identify promising ligands for tau-PHF. It is exciting to see progress in this field, and we hope to help introduce some drugs that could help prevent or at least alleviate this dreaded disease.
Mannix Balanay
Read the Original
This page is a summary of: Tau fibril with membrane lipids: Insight from computational modeling and simulations, PLoS ONE, October 2021, PLOS,
DOI: 10.1371/journal.pone.0258692.
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