Canonical and non-canonical autophagy pathways in microglia.

Besides the ubiquitin-proteasome-system, autophagy is a major degradation pathway within cells. It delivers invading pathogens, damaged organelles, aggregated proteins and other macromolecules from the cytosol to the lysosome for bulk degradation. This so-called canonical autophagy activity contributes to the maintenance of organelle, protein and metabolite homeostasis as well as innate immunity. Over the past years, numerous studies rapidly deepened our knowledge on the autophagy machinery and its regulation; driven by the fact that impairment of autophagy is associated with several human pathologies including cancer, immune diseases and neurodegenerative disorders. Unexpectedly, components of the autophagic machinery were also found to participate in various processes that did not involve lysosomal delivery of cytosolic constituents. These functions are hereafter defined as non-canonical autophagy. Regarding neurodegenerative diseases, most research was performed in neurons, while for a long-time microglia received considerably less attention. Concomitant with the notion that microglia greatly contribute to brain health, the understanding of the role of autophagy in microglia expanded. To facilitate an overview of the current knowledge, we present herein the fundamentals as well as the recent advances of canonical and non-canonical autophagy functions in microglia.