Copper-zinc superoxide dismutase (SOD1) is released by microglial cells and confers neuroprotection against 6-OHDA neurotoxicity

Neuro-Signals
Elisabetta PolazziBarbara Monti

Abstract

Microglial-neuronal interactions are essential for brain physiopathology. In this framework, recent data have changed the concept of microglia from essentially macrophagic cells to crucial elements in maintaining neuronal homeostasis and function through the release of neuroprotective molecules. Using proteomic analysis, here we identify copper-zinc superoxide dismutase (SOD1) as a protein produced and released by cultured rat primary microglia. Evidence for a neuroprotective role of microglia-derived SOD1 resulted from experiments in which primary cerebellar granule neurons (CGNs) were exposed to the dopaminergic toxin 6-hydroxydopamine (6-OHDA). Microglial conditioned medium, in which SOD1 had accumulated, protected CGNs from degeneration, and neuroprotection was abrogated by SOD1 inhibitors. These effects were replicated when exogenous SOD1 was added to a nonconditioned medium. SOD1 neuroprotective action was mediated by increased cell calcium from an external source. Further experiments demonstrated the specificity of SOD1 neuroprotection against 6-OHDA compared to other types of neurotoxic challenges. SOD1, constitutively produced and released by microglia through a lysosomal secretory pathway, is identified here for the f...Continue Reading

Citations

Jul 18, 2015·Journal of Neuropathology and Experimental Neurology·Elisabetta PolazziBarbara Monti
Mar 29, 2014·Oxidative Medicine and Cellular Longevity·Sergio MontesCamilo Rios
Dec 15, 2016·Frontiers in Physiology·Paolo MondolaMariarosaria Santillo
Apr 5, 2018·Toxicological Sciences : an Official Journal of the Society of Toxicology·Haitao YuXifei Yang
May 17, 2017·Critical Reviews in Toxicology·Alan BoobisHeli Miriam Hollnagel
Jun 24, 2017·Frontiers in Aging Neuroscience·Emiliano Peña-AltamiraBarbara Monti
May 28, 2019·Nutritional Neuroscience·Sarah Ben YoussefMartin Lévesque
Aug 2, 2019·Food Science & Nutrition·Nadia MazzarellaMaria Antonietta Ciardiello
Mar 8, 2021·Journal of Autism and Developmental Disorders·Morten ThorsenTanja Maria Michel

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