Microglial lipid metabolism during physiological and pathological conditions

An important task of microglia is phagocytosis and the breakdown of dead cells as well as extracellularly deposited proteins and lipids. The presence of extracellular debris can remarkably increase in pathological conditions and with age. Due to the variety of different cell types present in the CNS with each cell type expressing a specific repertoire of proteins, microglia must be able to adapt their catabolism to the phagocytosed material in order to avoid intracellular accumulation of the ingested lipids. An insufficient degradation of ingested material can cause morphological changes and the activation of microglia. This is the case, for example, in neurodegenerative pathologies such as Alzheimer's disease. Accordingly, activated microglia contribute to neurotoxicity and disease progression. In this research project, we aim to increase the catabolic activities of microglia, which then allows for the complete digestion of intracellularly stored lipids and thereby reduces microglial immune activation. The results may help to identify new therapeutic intervention strategies for neurodegenerative diseases such as Alzheimer's disease.