• J Sábado, A Casanovas, H Rodrigo, G Arqué, and J E Esquerda.
• Universitat de Lleida, Facultat de Medicina-IRBLLEIDA, Departament de Medicina Experimental, Unitat de Neurobiologia Cel·lular, Avda Rovira Roure 80, 25198 Lleida, Catalonia, Spain.
• Neuroscience. 2015 Dec 3; 310: 38-50.

AbstractPrevious 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.Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

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