Next Article in Journal
A Mathematical Model of Lysosomal Ion Homeostasis Points to Differential Effects of Cl− Transport in Ca2+ Dynamics
Next Article in Special Issue
Beta-Aminoisobutyric Acid Inhibits Hypothalamic Inflammation by Reversing Microglia Activation
Previous Article in Journal
Inhibition of Rho-Kinase Downregulates Th17 Cells and Ameliorates Hepatic Fibrosis by Schistosoma japonicum Infection
Previous Article in Special Issue
Alzheimer’s Disease Research Using Human Microglia
 
Search for Articles:
Title / Keyword
Author / Affiliation
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
Journals
Cells
Volume 8
Issue 10
10.3390/cells8101261
cells-logo
Submit to this Journal Review for this Journal Edit a Special Issue
► Article Menu

Article Menu

share announcement question_answer thumb_up
...
textsms
...
Article

The S100A4 Transcriptional Inhibitor Niclosamide Reduces Pro-Inflammatory and Migratory Phenotypes of Microglia: Implications for Amyotrophic Lateral Sclerosis

by
Alessia Serrano
1,†,
Savina Apolloni
2,†,
Simona Rossi
2,3,
Serena Lattante
4,5,
Mario Sabatelli
6,7,8,
Mina Peric
9,
Pavle Andjus
9,
Fabrizio Michetti
1,
Maria Teresa Carrì
2,
Mauro Cozzolino
3 and
Nadia D’Ambrosi
2,*
1
Institute of Anatomy and Cell Biology, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
2
Department of Biology, University of Rome “Tor Vergata”, 00133 Rome, Italy
3
Institute of Translational Pharmacology, CNR, 00133 Rome, Italy
4
Unità Operativa Complessa di Genetica Medica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
5
Istituto di Medicina Genomica, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
6
Unità Operativa Complessa di Neurologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
7
Centro Clinico NEMO, 00168 Rome, Italy
8
Istituto di Neurologia, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
9
Institute of Physiology and Biochemistry “Ivan Djaja”, Faculty of Biology, University of Belgrade, 11000 Belgrade, Serbia
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cells 2019, 8(10), 1261; https://doi.org/10.3390/cells8101261
Received: 30 August 2019 / Revised: 11 October 2019 / Accepted: 14 October 2019 / Published: 16 October 2019
(This article belongs to the Special Issue Microglia in Neurodegenerative Diseases)
View Full-Text Download PDF
Browse Figures

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. View Full-Text
Keywords: ALS; astrocytes; fibroblasts; microglia; mTOR; neurodegeneration; neuroinflammation; NF-κB; niclosamide; S100A4 ALS; astrocytes; fibroblasts; microglia; mTOR; neurodegeneration; neuroinflammation; NF-κB; niclosamide; S100A4
►▼ Show Figures

Figure 1

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
SciFeed

Share and Cite

MDPI and ACS Style

Serrano, A.; Apolloni, S.; Rossi, S.; Lattante, S.; Sabatelli, M.; Peric, M.; Andjus, P.; Michetti, F.; Carrì, M.T.; 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, 8, 1261. https://doi.org/10.3390/cells8101261

AMA Style

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; 8(10):1261. https://doi.org/10.3390/cells8101261

Chicago/Turabian Style

Serrano, Alessia, Savina Apolloni, Simona Rossi, Serena Lattante, Mario Sabatelli, Mina Peric, Pavle Andjus, Fabrizio Michetti, Maria T. Carrì, Mauro Cozzolino, and Nadia D’Ambrosi. 2019. "The S100A4 Transcriptional Inhibitor Niclosamide Reduces Pro-Inflammatory and Migratory Phenotypes of Microglia: Implications for Amyotrophic Lateral Sclerosis" Cells 8, no. 10: 1261. https://doi.org/10.3390/cells8101261

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Metrics

Article Access Map by Country/Region

1
Back to TopTop