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Fabbrizio P, Amadio S, Apolloni S, et al. P2X7 Receptor Activation Modulates Autophagy in SOD1-G93A Mouse Microglia. Front Cell Neurosci. 2017;11:249doi: 10.3389/fncel.2017.00249.
Fabbrizio, P., Amadio, S., Apolloni, S., & Volonté, C. (2017). P2X7 Receptor Activation Modulates Autophagy in SOD1-G93A Mouse Microglia. Frontiers in cellular neuroscience, 11249. https://doi.org/10.3389/fncel.2017.00249
Fabbrizio, Paola, et al. "P2X7 Receptor Activation Modulates Autophagy in SOD1-G93A Mouse Microglia." Frontiers in cellular neuroscience vol. 11 (2017): 249. doi: https://doi.org/10.3389/fncel.2017.00249
Fabbrizio P, Amadio S, Apolloni S, Volonté C. P2X7 Receptor Activation Modulates Autophagy in SOD1-G93A Mouse Microglia. Front Cell Neurosci. 2017 Aug 21;11:249. doi: 10.3389/fncel.2017.00249. eCollection 2017. PMID: 28871219; PMCID: PMC5566572.
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Front Cell Neurosci. 2017 Aug 21;11:249. doi: 10.3389/fncel.2017.00249. eCollection 2017.

P2X7 Receptor Activation Modulates Autophagy in SOD1-G93A Mouse Microglia.

Frontiers in cellular neuroscience

Paola Fabbrizio, Susanna Amadio, Savina Apolloni, Cinzia Volonté

Affiliations

  1. IRCCS Santa Lucia Foundation, Experimental NeuroscienceRome, Italy.
  2. Department of Systems Medicine, Tor Vergata UniversityRome, Italy.
  3. CNR, Institute of Cell Biology and NeurobiologyRome, Italy.

PMID: 28871219 PMCID: PMC5566572 DOI: 10.3389/fncel.2017.00249

Abstract

Autophagy and inflammation play determinant roles in the pathogenesis of Amyotrophic Lateral Sclerosis (ALS), an adult-onset neurodegenerative disease characterized by deterioration and final loss of upper and lower motor neurons (MN) priming microglia to sustain neuroinflammation and a vicious cycle of neurodegeneration. Given that extracellular ATP through P2X7 receptor constitutes a neuron-to-microglia alarm signal implicated in ALS, and that P2X7 affects autophagy in immune cells, we have investigated if autophagy can be directly triggered by P2X7 activation in primary microglia from superoxide dismutase 1 (SOD1)-G93A mice. We report that P2X7 enhances the expression of the autophagic marker microtubule-associated protein 1 light chain 3 (LC3)-II, via mTOR pathway and concomitantly with modulation of anti-inflammatory M2 microglia markers. We also demonstrate that the autophagic target SQSTM1/p62 is decreased in SOD1-G93A microglia after a short stimulation of P2X7, but increased after a sustained challenge. These effects are prevented by the P2X7 antagonist A-804598, and the autophagy/phosphoinositide-3-kinase inhibitor wortmannin (WM). Finally, a chronic

Keywords: ALS; ATP; BzATP; LC3B-II; P2X7; microglia

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