Please use this identifier to cite or link to this item: https://biore.bio.bg.ac.rs/handle/123456789/3696
Title: The S100A4 Transcriptional Inhibitor Niclosamide Reduces Pro-Inflammatory and Migratory Phenotypes of Microglia: Implications for Amyotrophic Lateral Sclerosis
Authors: Serrano, Alessia
Apolloni, Savina
Rossi, Simona
Lattante, Serena
Sabatelli, Mario
Peric, Mina 
Andjus, Pavle 
Michetti, Fabrizio
Carrì, Maria Teresa
Cozzolino, Mauro
D’Ambrosi, Nadia
Keywords: ALS;NF-κB;S100A4;astrocytes;fibroblasts;mTOR;microglia;neurodegeneration;neuroinflammation;niclosamide
Issue Date: 16-Oct-2019
Rank: M21
Citation: Serrano A, Apolloni S, Rossi S, Lattante S, Sabatelli M, Peric M, Andjus P, Michetti F, Carrì MT, Cozzolino M, D'Ambrosi N. The S100A4 Transcriptional Inhibitor Niclosamide Reduces Pro-Inflammatory and Migratory Phenotypes of Microglia: Implications for Amyotrophic Lateral Sclerosis. Cells. 2019 Oct 16;8(10):1261. doi: 10.3390/cells8101261. PMID: 31623154; PMCID: PMC6829868.
Journal: Cells
Abstract: 
S100A4, belonging to a large multifunctional S100 protein family, is a Ca2+-binding protein with a significant role in stimulating the motility of cancer and immune cells, as well as in promoting pro-inflammatory properties in different cell types. In the CNS, there is limited information concerning S100A4 presence and function. In this study, we analyzed the expression of S100A4 and the effect of the S100A4 transcriptional inhibitor niclosamide in murine activated primary microglia. We found that S100A4 was strongly up-regulated in reactive microglia and that niclosamide prevented NADPH oxidase 2, mTOR (mammalian target of rapamycin), and NF-κB (nuclear factor-kappa B) increase, cytoskeletal rearrangements, migration, and phagocytosis. Furthermore, we found that S100A4 was significantly up-regulated in astrocytes and microglia in the spinal cord of a transgenic rat SOD1-G93A model of amyotrophic lateral sclerosis. Finally, we demonstrated the increased expression of S100A4 also in fibroblasts derived from amyotrophic lateral sclerosis (ALS) patients carrying SOD1 pathogenic variants. These results ascribe S100A4 as a marker of microglial reactivity, suggesting the contribution of S100A4-regulated pathways to neuroinflammation, and identify niclosamide as a possible drug in the control and attenuation of reactive phenotypes of microglia, thus opening the way to further investigation for a new application in neurodegenerative conditions.
URI: https://biore.bio.bg.ac.rs/handle/123456789/3696
ISSN: 2073-4409
DOI: 10.3390/cells8101261
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