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Mediators of Inflammation
Volume 2017 (2017), Article ID 1626204, 14 pages
https://doi.org/10.1155/2017/1626204
Research Article

The Astrocytic S100B Protein with Its Receptor RAGE Is Aberrantly Expressed in SOD1G93A Models, and Its Inhibition Decreases the Expression of Proinflammatory Genes

1Institute of Anatomy and Cell Biology, Università Cattolica del Sacro Cuore, Rome, Italy
2Institute of Physiology and Biochemistry, Faculty of Biology, University of Belgrade, Belgrade, Serbia
3Department of Biology, University of Rome “Tor Vergata”, Rome, Italy
4IRCCS San Raffaele Scientific Institute, Università Vita-Salute San Raffaele, Milan, Italy

Correspondence should be addressed to Nadia D’Ambrosi; ti.2amorinu@isorbmad.aidan and Fabrizio Michetti; ti.ttacinu@ittehcim.oizirbaf

Received 21 February 2017; Accepted 30 April 2017; Published 20 June 2017

Academic Editor: Thomas Möller

Copyright © 2017 Alessia Serrano et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Neuroinflammation is one of the major players in amyotrophic lateral sclerosis (ALS) pathogenesis, and astrocytes are significantly involved in this process. The astrocytic protein S100B can be released in pathological states activating the receptor for advanced glycation end products (RAGE). Different indications point to an aberrant expression of S100B and RAGE in ALS. In this work, we observed that S100B and RAGE are progressively and selectively upregulated in astrocytes of diseased rats with a tissue-specific timing pattern, correlated to the level of neurodegeneration. The expression of the full-length and soluble RAGE isoforms could also be linked to the degree of tissue damage. The mere presence of mutant SOD1 is able to increase the intracellular levels and release S100B from astrocytes, suggesting the possibility that an increased astrocytic S100B expression might be an early occurring event in the disease. Finally, our findings indicate that the protein may exert a proinflammatory role in ALS, since its inhibition in astrocytes derived from SOD1G93A mice limits the expression of reactivity-linked/proinflammatory genes. Thus, our results propose the S100B-RAGE axis as an effective contributor to the pathogenesis of the disease, suggesting its blockade as a rational target for a therapeutic intervention in ALS.