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Title: The antigen-binding fragment of human gamma immunoglobulin prevents amyloid beta-peptide folding into beta-sheet to form oligomers
Author: Valls Comamala, Victòria
Guivernau, Biuse
Bonet, Jaume
Puig, Marta
Peralvarez Marin, Alex
Palomer, Ernest
Fernàndez Busquets, Xavier
Altafaj, Xavier
Tajes, Marta
Puig Pijoan, Albert
Vicente, Rubén
Oliva, Baldomero
Munoz, Francisco J.
Keywords: Malaltia d'Alzheimer
Malalties neurodegeneratives
Alzheimer's disease
Neurodegenerative Diseases
Issue Date: 13-Apr-2017
Publisher: Impact Journals
Abstract: The amyloid beta-peptide (Abeta) plays a leading role in Alzheimer's disease (AD) physiopathology. Even though monomeric forms of Abeta are harmless to cells, Abeta can aggregate into beta-sheet oligomers and fibrils, which are both neurotoxic. Therefore, one of the main therapeutic approaches to cure or delay AD onset and progression is targeting Abeta aggregation. In the present study, we show that a pool of human gamma immunoglobulins (IgG) protected cortical neurons from the challenge with Abeta oligomers, as assayed by MTT reduction, caspase-3 activation and cytoskeleton integrity. In addition, we report the inhibitory effect of IgG on Abeta aggregation, as shown by Thioflavin T assay, size exclusion chromatography and atomic force microscopy. Similar results were obtained with Palivizumab, a human anti-sincitial virus antibody. In order to dissect the important domains, we cleaved the pool of human IgG with papain to obtain Fab and Fc fragments. Using these cleaved fragments, we functionally identified Fab as the immunoglobulin fragment inhibiting Abeta aggregation, a result that was further confirmed by an in silico structural model. Interestingly, bioinformatic tools show a highly conserved structure able to bind amyloid in the Fab region. Overall, our data strongly support the inhibitory effect of human IgG on Abeta aggregation and its neuroprotective role.
Note: Reproducció del document publicat a:
It is part of: Oncotarget, 2017, vol. , num. , p. Ahead of print
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ISSN: 1949-2553
Appears in Collections:Articles publicats en revistes (ISGlobal)

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