Martín Calvelo (USC) — Impact of Lipid Cell Composition on Beta-Amyloid Aggregation: Exploring Novel Therapeutic Targets for Alzheimer's Disease
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📋 "Impact of Lipid Cell Composition on Beta-Amyloid Aggregation: Exploring Novel Therapeutic Targets for Alzheimer's Disease" led by Martín Calvelo Souto from Universidade de Santiago de Compostela
Alzheimer’s disease is a neurodegenerative disorder characterized by cognitive decline and memory loss, primarily associated with beta-amyloid (Aβ) aggregation. However, current drugs targeting Aβ fibrils still have uncertain efficacy, highlighting the need for new strategies.
Since changes in brain cell lipid profiles are associated with Alzheimer's progression, one emerging path is the study of lipid membrane composition. Particularly, the Aβlina project studies how different lipid compositions influence Aβ aggregation by means of Coarse-Grained Molecular Dynamics.
🖥️ Thanks to RES supercomputer #FinisTerraeIII from CESGA, the team performed over 700 simulations of neuronal membrane models, enabling the exploration of large-scale membrane–Aβ interactions.
The results revealed that gangliosides enhance Aβ deposition 10 times more than without them. They also found that a key driver of this interaction is the electrostatic interaction between N-acetylneuraminic acid from gangliosides and positively charged amino acids in Aβ.
From these results, the team identified potential strategies to develop new therapeutic possibilities:
🔹 Modulating ganglioside levels
🔹 Preventing their clustering in lipid rafts
🔹 Inhibiting their interaction with Aβ
📸 The image shows the initial (left) and final (right) snapshots of the simulation, displaying Aβ interactions with different lipid membrane compositions — one with gangliosides (bottom) and another without (top).