The S100A4 Transcriptional Inhibitor Niclosamide Reduces Pro-Inflammatory and Migratory Phenotypes of Microglia: Implications for Amyotrophic Lateral Sclerosis
Autori
Serrano, AlessiaApolloni, Savina
Rossi, Simona
Lattante, Serena
Sabatelli, Mario
Perić, Mina
Andjus, Pavle R.
Michetti, Fabrizio
Carri, Maria Teresa
Cozzolino, Mauro
D'Ambrosi, Nadia
Članak u časopisu (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
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-kappa B (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 i...n 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.
Ključne reči:
S100A4 / niclosamide / NF-kappa B / neuroinflammation / neurodegeneration / mTOR / microglia / fibroblasts / astrocytes / ALSIzvor:
Cells, 2019, 8, 10Izdavač:
- MDPI, Basel
Finansiranje / projekti:
- FFABR-MIUR
- AriSLA (SpliceALS grant)
- PRIN-MIUR [PRIN-2015LFPNMN]
- Biomarkeri u neurodegenerativnim i malignim procesima (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41005)
DOI: 10.3390/cells8101261
ISSN: 2073-4409
PubMed: 31623154
WoS: 000497336400150
Scopus: 2-s2.0-85077253312
Institucija/grupa
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Serrano, Alessia AU - Apolloni, Savina AU - Rossi, Simona AU - Lattante, Serena AU - Sabatelli, Mario AU - Perić, Mina AU - Andjus, Pavle R. AU - Michetti, Fabrizio AU - Carri, Maria Teresa AU - Cozzolino, Mauro AU - D'Ambrosi, Nadia PY - 2019 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/1220 AB - 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-kappa B (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. PB - MDPI, Basel T2 - Cells T1 - The S100A4 Transcriptional Inhibitor Niclosamide Reduces Pro-Inflammatory and Migratory Phenotypes of Microglia: Implications for Amyotrophic Lateral Sclerosis IS - 10 VL - 8 DO - 10.3390/cells8101261 ER -
@article{ author = "Serrano, Alessia and Apolloni, Savina and Rossi, Simona and Lattante, Serena and Sabatelli, Mario and Perić, Mina and Andjus, Pavle R. and Michetti, Fabrizio and Carri, Maria Teresa and Cozzolino, Mauro and D'Ambrosi, Nadia", year = "2019", 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-kappa B (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.", publisher = "MDPI, Basel", journal = "Cells", title = "The S100A4 Transcriptional Inhibitor Niclosamide Reduces Pro-Inflammatory and Migratory Phenotypes of Microglia: Implications for Amyotrophic Lateral Sclerosis", number = "10", volume = "8", doi = "10.3390/cells8101261" }
Serrano, A., Apolloni, S., Rossi, S., Lattante, S., Sabatelli, M., Perić, M., Andjus, P. R., Michetti, F., Carri, M. T., Cozzolino, M.,& D'Ambrosi, N.. (2019). The S100A4 Transcriptional Inhibitor Niclosamide Reduces Pro-Inflammatory and Migratory Phenotypes of Microglia: Implications for Amyotrophic Lateral Sclerosis. in Cells MDPI, Basel., 8(10). https://doi.org/10.3390/cells8101261
Serrano A, Apolloni S, Rossi S, Lattante S, Sabatelli M, Perić M, Andjus PR, Michetti F, Carri MT, Cozzolino M, D'Ambrosi N. The S100A4 Transcriptional Inhibitor Niclosamide Reduces Pro-Inflammatory and Migratory Phenotypes of Microglia: Implications for Amyotrophic Lateral Sclerosis. in Cells. 2019;8(10). doi:10.3390/cells8101261 .
Serrano, Alessia, Apolloni, Savina, Rossi, Simona, Lattante, Serena, Sabatelli, Mario, Perić, Mina, Andjus, Pavle R., Michetti, Fabrizio, Carri, Maria Teresa, Cozzolino, Mauro, D'Ambrosi, Nadia, "The S100A4 Transcriptional Inhibitor Niclosamide Reduces Pro-Inflammatory and Migratory Phenotypes of Microglia: Implications for Amyotrophic Lateral Sclerosis" in Cells, 8, no. 10 (2019), https://doi.org/10.3390/cells8101261 . .