| Autor: |
Dabrowska S; Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy.; NeuroRepair Department, Mossakowski Medical Research Institute, Polish Academy of Sciences, Pawinskiego Street 5, 02-106 Warsaw, Poland., Turano E; Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy., Scambi I; Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy., Virla F; Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy., Nodari A; Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy., Pezzini F; Department of Surgery, Dentistry, Paediatrics and Gynaecology (Child Neurology and Psychiatry), University of Verona, 37134 Verona, Italy., Galiè M; Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy., Bonetti B; Neurology Unit, Azienda Ospedaliera Universitaria Integrata, 37126 Verona, Italy., Mariotti R; Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy. |
| Abstrakt: |
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive degeneration of upper and lower motor neurons (MNs) in the brain and spinal cord, leading to progressive paralysis and death. Increasing evidence indicates that neuroinflammation plays an important role in ALS's pathogenesis and disease progression. Neuroinflammatory responses, primarily driven by activated microglia and astrocytes, and followed by infiltrating peripheral immune cells, contribute to exacerbate/accelerate MN death. In particular, the role of the microglia in ALS remains unclear, partly due to the lack of experimental models that can fully recapitulate the complexity of ALS's pathology. In this study, we developed and characterized a microglial cell line, SIM-A9-expressing human mutant protein Cu + /Zn + superoxide dismutase_1 (SIM-A9hSOD1(G93A)), as a suitable model in vitro mimicking the microglia activity in ALS. The expression of hSOD1(G93A) in SIM-A9 cells induced a change in their metabolic activity, causing polarization into a pro-inflammatory phenotype and enhancing reactive oxygen species production, which is known to activate cell death processes and apoptosis. Afterward, we used our microglial model as an experimental set-up to investigate the therapeutic action of extracellular vesicles isolated from adipose mesenchymal stem cells (ASC-EVs). ASC-EVs represent a promising therapeutic treatment for ALS due to their neuroprotective and immunomodulatory properties. Here, we demonstrated that treatment with ASC-EVs is able to modulate activated ALS microglia, reducing their metabolic activity and polarizing their phenotype toward an anti-inflammatory one through a mechanism of reduction of reactive oxygen species. |
