Title: The role of autophagy in microglia under homeostatic and neuropathological condition
Autophagy is an intracellular degradation system essential for cellular homeostasis. This process acts as a housekeeper by eliminating defective proteins and organelles, preventing protein aggregate accumulation and removing pathogens, and is increasingly considered to be key regulator of (neuro)inflammation. Microglia, the macrophages of the central nervous system (CNS), are involved in the maintenance of CNS homeostasis. Immune activation of microglia plays an important role in many neurodegenerative diseases, including Multiple Sclerosis (MS). MS is a prevalent auto-immune disorder of the CNS characterized by chronic neuroinflammation, demyelination and neuronal loss. Preliminary data in a mouse model for MS revealed significant changes in expression of autophagy genes at specific disease stages.
This project aims to understand 1) the role of autophagy in microglia function under control, homeostatic conditions and 2) how (disturbed) microglial autophagy contributes to neuropathology in general and MS in particular. We hypothesize that autophagy in microglia is essential for the clearance of cell debris which may be caused by inflammation. Autophagy in microglia may contribute to this process and impairment of autophagy in microglia in MS may hinder debris clearance, resulting in damaged remyelination and enhancement of neuroinflammation.
Funded by the Graduate School of Medical Sciences