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Proteome-wide characterization of signalling interactions in the hippocampal CA4/DG subfield of patients with Alzheimer’s disease
Alzheimer’s disease (AD) is the most common form of dementia; however, mechanisms and biomarkers remain unclear. Here, we examined hippocampal CA4 and dentate gyrus subfields, which are less studied in the context of AD pathology, in post-mortem AD and control tissue to identify possible biomarkers....
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4462342/ https://www.ncbi.nlm.nih.gov/pubmed/26059363 http://dx.doi.org/10.1038/srep11138 |
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author | Ho Kim, Jae Franck, Julien Kang, Taewook Heinsen, Helmut Ravid, Rivka Ferrer, Isidro Hee Cheon, Mi Lee, Joo-Yong Shin Yoo, Jong Steinbusch, Harry W Salzet, Michel Fournier, Isabelle Mok Park, Young |
author_facet | Ho Kim, Jae Franck, Julien Kang, Taewook Heinsen, Helmut Ravid, Rivka Ferrer, Isidro Hee Cheon, Mi Lee, Joo-Yong Shin Yoo, Jong Steinbusch, Harry W Salzet, Michel Fournier, Isabelle Mok Park, Young |
author_sort | Ho Kim, Jae |
collection | PubMed |
description | Alzheimer’s disease (AD) is the most common form of dementia; however, mechanisms and biomarkers remain unclear. Here, we examined hippocampal CA4 and dentate gyrus subfields, which are less studied in the context of AD pathology, in post-mortem AD and control tissue to identify possible biomarkers. We performed mass spectrometry-based proteomic analysis combined with label-free quantification for identification of differentially expressed proteins. We identified 4,328 proteins, of which 113 showed more than 2-fold higher or lower expression in AD hippocampi than in control tissues. Five proteins were identified as putative AD biomarkers (MDH2, PCLO, TRRAP, YWHAZ, and MUC19 isoform 5) and were cross-validated by immunoblotting, selected reaction monitoring, and MALDI imaging. We also used a bioinformatics approach to examine upstream signalling interactions of the 113 regulated proteins. Five upstream signalling (IGF1, BDNF, ZAP70, MYC, and cyclosporin A) factors showed novel interactions in AD hippocampi. Taken together, these results demonstrate a novel platform that may provide new strategies for the early detection of AD and thus its diagnosis. |
format | Online Article Text |
id | pubmed-4462342 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-44623422015-06-12 Proteome-wide characterization of signalling interactions in the hippocampal CA4/DG subfield of patients with Alzheimer’s disease Ho Kim, Jae Franck, Julien Kang, Taewook Heinsen, Helmut Ravid, Rivka Ferrer, Isidro Hee Cheon, Mi Lee, Joo-Yong Shin Yoo, Jong Steinbusch, Harry W Salzet, Michel Fournier, Isabelle Mok Park, Young Sci Rep Article Alzheimer’s disease (AD) is the most common form of dementia; however, mechanisms and biomarkers remain unclear. Here, we examined hippocampal CA4 and dentate gyrus subfields, which are less studied in the context of AD pathology, in post-mortem AD and control tissue to identify possible biomarkers. We performed mass spectrometry-based proteomic analysis combined with label-free quantification for identification of differentially expressed proteins. We identified 4,328 proteins, of which 113 showed more than 2-fold higher or lower expression in AD hippocampi than in control tissues. Five proteins were identified as putative AD biomarkers (MDH2, PCLO, TRRAP, YWHAZ, and MUC19 isoform 5) and were cross-validated by immunoblotting, selected reaction monitoring, and MALDI imaging. We also used a bioinformatics approach to examine upstream signalling interactions of the 113 regulated proteins. Five upstream signalling (IGF1, BDNF, ZAP70, MYC, and cyclosporin A) factors showed novel interactions in AD hippocampi. Taken together, these results demonstrate a novel platform that may provide new strategies for the early detection of AD and thus its diagnosis. Nature Publishing Group 2015-06-10 /pmc/articles/PMC4462342/ /pubmed/26059363 http://dx.doi.org/10.1038/srep11138 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Ho Kim, Jae Franck, Julien Kang, Taewook Heinsen, Helmut Ravid, Rivka Ferrer, Isidro Hee Cheon, Mi Lee, Joo-Yong Shin Yoo, Jong Steinbusch, Harry W Salzet, Michel Fournier, Isabelle Mok Park, Young Proteome-wide characterization of signalling interactions in the hippocampal CA4/DG subfield of patients with Alzheimer’s disease |
title | Proteome-wide characterization of signalling interactions in the hippocampal CA4/DG subfield of patients with Alzheimer’s disease |
title_full | Proteome-wide characterization of signalling interactions in the hippocampal CA4/DG subfield of patients with Alzheimer’s disease |
title_fullStr | Proteome-wide characterization of signalling interactions in the hippocampal CA4/DG subfield of patients with Alzheimer’s disease |
title_full_unstemmed | Proteome-wide characterization of signalling interactions in the hippocampal CA4/DG subfield of patients with Alzheimer’s disease |
title_short | Proteome-wide characterization of signalling interactions in the hippocampal CA4/DG subfield of patients with Alzheimer’s disease |
title_sort | proteome-wide characterization of signalling interactions in the hippocampal ca4/dg subfield of patients with alzheimer’s disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4462342/ https://www.ncbi.nlm.nih.gov/pubmed/26059363 http://dx.doi.org/10.1038/srep11138 |
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