title: Autophagy and Microglia: Novel Partners in Neurodegeneration and Aging.
abstract: Autophagy is emerging as a core regulator of Central Nervous System (CNS) aging and neurodegeneration. In the brain, it has mostly been studied in neurons, where the delivery of toxic molecules and organelles to the lysosome by autophagy is crucial for neuronal health and survival. However, we propose that the (dys)regulation of autophagy in microglia also affects innate immune functions such as phagocytosis and inflammation, which in turn contribute to the pathophysiology of aging and neurodegenerative diseases. Herein, we first describe the basic concepts of autophagy and its regulation, discuss key aspects for its accurate monitoring at the experimental level, and summarize the evidence linking autophagy impairment to CNS senescence and disease. We focus on acute, chronic, and autoimmunity-mediated neurodegeneration, including ischemia/stroke, Alzheimer's, Parkinson's, and Huntington's diseases, and multiple sclerosis. Next, we describe the actual and potential impact of autophagy on microglial phagocytic and inflammatory function. Thus, we provide evidence of how autophagy may affect microglial phagocytosis of apoptotic cells, amyloid-β, synaptic material, and myelin debris, and regulate the progression of age-associated neurodegenerative diseases. We also discuss data linking autophagy to the regulation of the microglial inflammatory phenotype, which is known to contribute to age-related brain dysfunction. Overall, we update the current knowledge of autophagy and microglia, and highlight as yet unexplored mechanisms whereby autophagy in microglia may contribute to CNS disease and senescence.
authors.affiliation: Achucarro Basque Center for Neuroscience, 48170 Zamudio, Spain. ainhoa.plaza@achucarro.org.
authors.forename: Ainhoa
authors.initials: A
authors.lastname: Plaza-Zabala
authors.affiliation: Achucarro Basque Center for Neuroscience, 48170 Zamudio, Spain. virginiasierra1@gmail.com.
authors.forename: Virginia
authors.initials: V
authors.lastname: Sierra-Torre
authors.affiliation: Achucarro Basque Center for Neuroscience, 48170 Zamudio, Spain. a.sierra@ikerbasque.org.|Department of Neurosciences, University of the Basque Country EHU/UPV, 48940 Leioa, Spain. a.sierra@ikerbasque.org.|Ikerbasque Foundation, 48013 Bilbao, Spain. a.sierra@ikerbasque.org.
authors.forename: Amanda
authors.initials: A
authors.lastname: Sierra
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D001343:Autophagy; D002490:Central Nervous System / Q000254:growth & development / Q000378:metabolism; D006801:Humans; D017628:Microglia / Q000166:cytology / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism*
keywords: aging; autophagy; inflammation; microglia; neurodegeneration; phagocytosis