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Neuroprotective Fragment C of Tetanus Toxin Modulates IL-6 in an ALS Mouse Model

1
Laboratory of Genetics and Biochemistry (LAGENBIO), Faculty of Veterinary, Institute for Health Research Aragon (IIS Aragón), AgriFood Institute of Aragon (IA2), Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), University of Zaragoza, Miguel Servet 177, 50013 Zaragoza, Spain
2
Institut de Neurociències and Departament de Bioquímica i de Biologia Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona (UAB) and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), 08193 Barcelona, Spain
*
Authors to whom correspondence should be addressed.
Toxins 2020, 12(5), 330; https://doi.org/10.3390/toxins12050330
Received: 25 March 2020 / Revised: 15 April 2020 / Accepted: 13 May 2020 / Published: 17 May 2020
Neuroinflammation plays a significant role in amyotrophic lateral sclerosis (ALS) pathology, leading to the development of therapies targeting inflammation in recent years. Our group has studied the tetanus toxin C-terminal fragment (TTC) as a therapeutic molecule, showing neuroprotective properties in the SOD1G93A mouse model. However, it is unknown whether TTC could have some effect on inflammation. The objective of this study was to assess the effect of TTC on the regulation of inflammatory mediators to elucidate its potential role in modulating inflammation occurring in ALS. After TTC treatment in SOD1G93A mice, levels of eotaxin-1, interleukin (IL)-2, IL-6 and macrophage inflammatory protein (MIP)-1 alpha (α) and galectin-1 were analyzed by immunoassays in plasma samples, whilst protein expression of caspase-1, IL-1β, IL-6 and NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) was measured in the spinal cord, extensor digitorum longus (EDL) muscle and soleus (SOL) muscle. The results showed reduced levels of IL-6 in spinal cord, EDL and SOL in treated SOD1G93A mice. In addition, TTC showed a different role in the modulation of NLRP3 and caspase-1 depending on the tissue analyzed. In conclusion, our results suggest that TTC could have a potential anti-inflammatory effect by reducing IL-6 levels in tissues drastically affected by the disease. However, further research is needed to study more in depth the anti-inflammatory effect of TTC in ALS. View Full-Text
Keywords: TTC; amyotrophic lateral sclerosis; inflammation; SOD1G93A mouse model TTC; amyotrophic lateral sclerosis; inflammation; SOD1G93A mouse model
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Moreno-Martinez, L.; de la Torre, M.; Muñoz, M.J.; Zaragoza, P.; Aguilera, J.; Calvo, A.C.; Osta, R. Neuroprotective Fragment C of Tetanus Toxin Modulates IL-6 in an ALS Mouse Model. Toxins 2020, 12, 330.

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