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VGF Protein and Its C-Terminal Derived Peptides in Amyotrophic Lateral Sclerosis: Human and Animal Model Studies
VGF mRNA is widely expressed in areas of the nervous system known to degenerate in Amyotrophic Lateral Sclerosis (ALS), including cerebral cortex, brainstem and spinal cord. Despite certain VGF alterations are reported in animal models, little information is available with respect to the ALS patient...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5063282/ https://www.ncbi.nlm.nih.gov/pubmed/27737014 http://dx.doi.org/10.1371/journal.pone.0164689 |
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author | Brancia, Carla Noli, Barbara Boido, Marina Boi, Andrea Puddu, Roberta Borghero, Giuseppe Marrosu, Francesco Bongioanni, Paolo Orrù, Sandro Manconi, Barbara D’Amato, Filomena Messana, Irene Vincenzoni, Federica Vercelli, Alessandro Ferri, Gian-Luca Cocco, Cristina |
author_facet | Brancia, Carla Noli, Barbara Boido, Marina Boi, Andrea Puddu, Roberta Borghero, Giuseppe Marrosu, Francesco Bongioanni, Paolo Orrù, Sandro Manconi, Barbara D’Amato, Filomena Messana, Irene Vincenzoni, Federica Vercelli, Alessandro Ferri, Gian-Luca Cocco, Cristina |
author_sort | Brancia, Carla |
collection | PubMed |
description | VGF mRNA is widely expressed in areas of the nervous system known to degenerate in Amyotrophic Lateral Sclerosis (ALS), including cerebral cortex, brainstem and spinal cord. Despite certain VGF alterations are reported in animal models, little information is available with respect to the ALS patients. We addressed VGF peptide changes in fibroblast cell cultures and in plasma obtained from ALS patients, in parallel with spinal cord and plasma samples from the G93A-SOD1 mouse model. Antisera specific for the C-terminal end of the human and mouse VGF proteins, respectively, were used in immunohistochemistry and enzyme-linked immunosorbent assay (ELISA), while gel chromatography and HPLC/ESI-MS/MS were used to identify the VGF peptides present. Immunoreactive VGF C-terminus peptides were reduced in both fibroblast and plasma samples from ALS patients in an advanced stage of the disease. In the G93A-SOD1 mice, the same VGF peptides were also decreased in plasma in the late-symptomatic stage, while showing an earlier down-regulation in the spinal cord. In immunohistochemistry, a large number of gray matter structures were VGF C-terminus immunoreactive in control mice (including nerve terminals, axons and a few perikarya identified as motoneurons), with a striking reduction already in the pre-symptomatic stage. Through gel chromatography and spectrometry analysis, we identified one form likely to be the VGF precursor as well as peptides containing the NAPP- sequence in all tissues studied, while in the mice and fibroblasts, we revealed also AQEE- and TLQP- peptides. Taken together, selective VGF fragment depletion may participate in disease onset and/or progression of ALS. |
format | Online Article Text |
id | pubmed-5063282 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-50632822016-11-04 VGF Protein and Its C-Terminal Derived Peptides in Amyotrophic Lateral Sclerosis: Human and Animal Model Studies Brancia, Carla Noli, Barbara Boido, Marina Boi, Andrea Puddu, Roberta Borghero, Giuseppe Marrosu, Francesco Bongioanni, Paolo Orrù, Sandro Manconi, Barbara D’Amato, Filomena Messana, Irene Vincenzoni, Federica Vercelli, Alessandro Ferri, Gian-Luca Cocco, Cristina PLoS One Research Article VGF mRNA is widely expressed in areas of the nervous system known to degenerate in Amyotrophic Lateral Sclerosis (ALS), including cerebral cortex, brainstem and spinal cord. Despite certain VGF alterations are reported in animal models, little information is available with respect to the ALS patients. We addressed VGF peptide changes in fibroblast cell cultures and in plasma obtained from ALS patients, in parallel with spinal cord and plasma samples from the G93A-SOD1 mouse model. Antisera specific for the C-terminal end of the human and mouse VGF proteins, respectively, were used in immunohistochemistry and enzyme-linked immunosorbent assay (ELISA), while gel chromatography and HPLC/ESI-MS/MS were used to identify the VGF peptides present. Immunoreactive VGF C-terminus peptides were reduced in both fibroblast and plasma samples from ALS patients in an advanced stage of the disease. In the G93A-SOD1 mice, the same VGF peptides were also decreased in plasma in the late-symptomatic stage, while showing an earlier down-regulation in the spinal cord. In immunohistochemistry, a large number of gray matter structures were VGF C-terminus immunoreactive in control mice (including nerve terminals, axons and a few perikarya identified as motoneurons), with a striking reduction already in the pre-symptomatic stage. Through gel chromatography and spectrometry analysis, we identified one form likely to be the VGF precursor as well as peptides containing the NAPP- sequence in all tissues studied, while in the mice and fibroblasts, we revealed also AQEE- and TLQP- peptides. Taken together, selective VGF fragment depletion may participate in disease onset and/or progression of ALS. Public Library of Science 2016-10-13 /pmc/articles/PMC5063282/ /pubmed/27737014 http://dx.doi.org/10.1371/journal.pone.0164689 Text en © 2016 Brancia et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Brancia, Carla Noli, Barbara Boido, Marina Boi, Andrea Puddu, Roberta Borghero, Giuseppe Marrosu, Francesco Bongioanni, Paolo Orrù, Sandro Manconi, Barbara D’Amato, Filomena Messana, Irene Vincenzoni, Federica Vercelli, Alessandro Ferri, Gian-Luca Cocco, Cristina VGF Protein and Its C-Terminal Derived Peptides in Amyotrophic Lateral Sclerosis: Human and Animal Model Studies |
title | VGF Protein and Its C-Terminal Derived Peptides in Amyotrophic Lateral Sclerosis: Human and Animal Model Studies |
title_full | VGF Protein and Its C-Terminal Derived Peptides in Amyotrophic Lateral Sclerosis: Human and Animal Model Studies |
title_fullStr | VGF Protein and Its C-Terminal Derived Peptides in Amyotrophic Lateral Sclerosis: Human and Animal Model Studies |
title_full_unstemmed | VGF Protein and Its C-Terminal Derived Peptides in Amyotrophic Lateral Sclerosis: Human and Animal Model Studies |
title_short | VGF Protein and Its C-Terminal Derived Peptides in Amyotrophic Lateral Sclerosis: Human and Animal Model Studies |
title_sort | vgf protein and its c-terminal derived peptides in amyotrophic lateral sclerosis: human and animal model studies |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5063282/ https://www.ncbi.nlm.nih.gov/pubmed/27737014 http://dx.doi.org/10.1371/journal.pone.0164689 |
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