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Adverse effects of a SOD1-peptide immunotherapy on SOD1(G93A) mouse slow model of amyotrophic lateral sclerosi

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Issue date
2015-12-01
Author
Sábado, J.
Casanovas i Llorens, Anna
Rodrigo, H.
Arque, Gloria
Esquerda Colell, Josep
Suggested citation
Sábado, J.; Casanovas i Llorens, Anna; Rodrigo, H.; Arque, Gloria; Esquerda Colell, Josep; . (2015) . Adverse effects of a SOD1-peptide immunotherapy on SOD1(G93A) mouse slow model of amyotrophic lateral sclerosi. Neuroscience, 2015, vol. 310, p. 38-50. https://doi.org/10.1016/j.neuroscience.2015.09.027.
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Abstract
Previous reports from our lab had shown that some anti-purinergic receptor P2X4 antibodies cross-reacted with misfolded forms of mutant Cu/Zn superoxide dismutase 1 (SOD1), linked to amyotrophic lateral sclerosis (ALS). Cross-reactivity could be caused by the abnormal exposure of an epitope located in the inner hydrophobic region of SOD1 that shared structural homology with the P2X4-immunizing peptide. We had previously raised antibodies against human SOD1 epitope mimicked by the P2X4 immunizing peptide. One of these antibodies, called AJ10, was able to recognize mutant/misfolded forms of ALS-linked mutant SOD1. Here, we used the AJ10 antigen as a vaccine to target neurotoxic species of mutant SOD1 in a slow mouse model of ALS. However, the obtained results showed no improvement in life span, disease onset or weight loss in treated animals; we observed an increased microglial neuroinflammatory response and high amounts of misfolded SOD1 accumulated within spinal cord neurons after AJ10 immunization. An increase of immunoglobulin G deposits was also found due to the treatment. Finally, a significantly worse clinical evolution was displayed by an impairment on motor function as a consequence of AJ10 peptide immunization
URI
http://hdl.handle.net/10459.1/49398
DOI
https://doi.org/10.1016/j.neuroscience.2015.09.027
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Neuroscience, 2015, vol. 310, p. 38-50
European research projects
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  • Articles publicats (Medicina Experimental) [323]
  • Articles publicats (Grup de Recerca en Neurobiologia Cel·lular) [19]
  • Articles publicats (IRBLleida) [1057]

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