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...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5063282?pdf=render |
| _version_ | 1811221238896394240 |
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| author | Carla Brancia Barbara Noli Marina Boido Andrea Boi Roberta Puddu Giuseppe Borghero Francesco Marrosu Paolo Bongioanni Sandro Orrù Barbara Manconi Filomena D'Amato Irene Messana Federica Vincenzoni Alessandro Vercelli Gian-Luca Ferri Cristina Cocco |
| author_facet | Carla Brancia Barbara Noli Marina Boido Andrea Boi Roberta Puddu Giuseppe Borghero Francesco Marrosu Paolo Bongioanni Sandro Orrù Barbara Manconi Filomena D'Amato Irene Messana Federica Vincenzoni Alessandro Vercelli Gian-Luca Ferri Cristina Cocco |
| author_sort | Carla Brancia |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T07:55:59Z |
| format | Article |
| id | doaj.art-ad59cfc36a4b4c04b1e1dfb9201ae777 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T07:55:59Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-ad59cfc36a4b4c04b1e1dfb9201ae7772022-12-22T03:41:29ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-011110e016468910.1371/journal.pone.0164689VGF Protein and Its C-Terminal Derived Peptides in Amyotrophic Lateral Sclerosis: Human and Animal Model Studies.Carla BranciaBarbara NoliMarina BoidoAndrea BoiRoberta PudduGiuseppe BorgheroFrancesco MarrosuPaolo BongioanniSandro OrrùBarbara ManconiFilomena D'AmatoIrene MessanaFederica VincenzoniAlessandro VercelliGian-Luca FerriCristina CoccoVGF 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.http://europepmc.org/articles/PMC5063282?pdf=render |
| spellingShingle | Carla Brancia Barbara Noli Marina Boido Andrea Boi Roberta Puddu Giuseppe Borghero Francesco Marrosu Paolo Bongioanni Sandro Orrù Barbara Manconi Filomena D'Amato Irene Messana Federica Vincenzoni Alessandro Vercelli Gian-Luca Ferri Cristina Cocco VGF Protein and Its C-Terminal Derived Peptides in Amyotrophic Lateral Sclerosis: Human and Animal Model Studies. PLoS ONE |
| 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 |
| url | http://europepmc.org/articles/PMC5063282?pdf=render |
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