Canonical and Noncanonical Autophagy Pathways in Microglia

ABSTRACT

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 do not involve lysosomal delivery of cytosolic constituents. These functions are defined as noncanonical 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, here we present the fundamentals as well as the recent advances of canonical and noncanonical autophagy functions in microglia.