Project R-16206

Greasy proteins driving maladaptive microglia function in Alzheimer's disease. (Research)

In Alzheimer's disease, microglia - the brain's immune cells - become imbalanced and contribute to inflammation and damage instead of protection. Recent studies show that disrupted lipid metabolism plays an important role in this process, and our findings suggest that S-acylation - the attachment of fats to proteins - contributes to these harmful changes in microglia. In this project, we investigate which enzymes involved in S-acylation become dysregulated, which proteins are affected as a result, and whether this process can be restored. To do so, we use advanced preclinical models, patient brain tissue, and innovative techniques to accurately measure S-acylation. In this way, we map changes in lipid processing and S-acylation in Alzheimer's disease and identify potential targets to make harmful microglia protective again. This knowledge may lead to new treatments that reduce brain inflammation and promote the recovery of brain functions.

01 January 2026 - 31 December 2028