A different vision of translational research in biomarker discovery: a pilot study on circulatory mitochondrial proteins as Parkinson’s disease potential biomarkers
Abstract Background The identification of circulating biomarkers that closely correlate with Parkinson’s Disease (PD) has failed several times in the past. Nevertheless, in this pilot study, a translational approach was conducted, allowing the evaluation of the plasma levels of two mitochondrial-rel...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-04-01
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| Series: | Translational Neurodegeneration |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s40035-020-00188-0 |
| _version_ | 1818776020678868992 |
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| author | Sandra I. Anjo Patrícia Valério dos Santos Luiza Rosado Graça Baltazar Inês Baldeiras Diana Pires Andreia Gomes Cristina Januário Miguel Castelo-Branco Mário Grãos Bruno Manadas |
| author_facet | Sandra I. Anjo Patrícia Valério dos Santos Luiza Rosado Graça Baltazar Inês Baldeiras Diana Pires Andreia Gomes Cristina Januário Miguel Castelo-Branco Mário Grãos Bruno Manadas |
| author_sort | Sandra I. Anjo |
| collection | DOAJ |
| description | Abstract Background The identification of circulating biomarkers that closely correlate with Parkinson’s Disease (PD) has failed several times in the past. Nevertheless, in this pilot study, a translational approach was conducted, allowing the evaluation of the plasma levels of two mitochondrial-related proteins, whose combination leads to a robust model with potential diagnostic value to discriminate the PD patients from matched controls. Methods The proposed translational approach was initiated by the analysis of secretomes from cells cultured under control or well-defined oxidative stress conditions, followed by the identification of proteins related to PD pathologic mechanisms that were altered between the two states. This pipeline was further translated into the analysis of undepleted plasma samples from 28 control and 31 PD patients. Results From the secretome analysis, several mitochondria-related proteins were found to be differentially released between control and stress conditions and to be able to distinguish the two secretomes. Similarly, two mitochondrial-related proteins were found to be significantly changed in a PD cohort compared to matched controls. Moreover, a linear discriminant model with potential diagnostic value to discriminate PD patients was obtained using the combination of these two proteins. Both proteins are associated with apoptotic mitochondrial changes, which may correspond to potential indicators of cell death. Moreover, one of these proteins, the VPS35 protein, was reported in plasma for the first time, and its quantification was only possible due to its previous identification in the secretome analysis. Conclusions In this work, an adaptation of a translational pipeline for biomarker selection was presented and transposed to neurological diseases, in the present case Parkinson’s Disease. The novelty and success of this pilot study may arise from the combination of: i) a translational research pipeline, where plasma samples are interrogated using knowledge previously obtained from the evaluation of cells’ secretome under oxidative stress; ii) the combined used of statistical analysis and an informed selection of candidates based on their link with relevant disease mechanisms, and iii) the use of SWATH-MS, an untargeted MS method that allows a complete record of the analyzed samples and a targeted data extraction of the quantitative values of proteins previously identified. |
| first_indexed | 2024-12-18T11:06:18Z |
| format | Article |
| id | doaj.art-8393de978cc645d984e7c48fcb444a26 |
| institution | Directory Open Access Journal |
| issn | 2047-9158 |
| language | English |
| last_indexed | 2024-12-18T11:06:18Z |
| publishDate | 2020-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Translational Neurodegeneration |
| spelling | doaj.art-8393de978cc645d984e7c48fcb444a262022-12-21T21:10:05ZengBMCTranslational Neurodegeneration2047-91582020-04-019111410.1186/s40035-020-00188-0A different vision of translational research in biomarker discovery: a pilot study on circulatory mitochondrial proteins as Parkinson’s disease potential biomarkersSandra I. Anjo0Patrícia Valério dos Santos1Luiza Rosado2Graça Baltazar3Inês Baldeiras4Diana Pires5Andreia Gomes6Cristina Januário7Miguel Castelo-Branco8Mário Grãos9Bruno Manadas10CNC - Center for Neuroscience and Cell Biology, University of CoimbraCentro de Investigação em Ciências da Saúde (CICS-UBI), Universidade da Beira InteriorCentro Hospitalar Cova da Beira, E.P.ECentro de Investigação em Ciências da Saúde (CICS-UBI), Universidade da Beira InteriorCNC - Center for Neuroscience and Cell Biology, University of CoimbraCoimbra Institute for Biomedical Imaging and Translational Research (CIBIT)Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT)Neurology Department, Centro Hospitalar e Universitário de CoimbraCoimbra Institute for Biomedical Imaging and Translational Research (CIBIT)CNC - Center for Neuroscience and Cell Biology, University of CoimbraCNC - Center for Neuroscience and Cell Biology, University of CoimbraAbstract Background The identification of circulating biomarkers that closely correlate with Parkinson’s Disease (PD) has failed several times in the past. Nevertheless, in this pilot study, a translational approach was conducted, allowing the evaluation of the plasma levels of two mitochondrial-related proteins, whose combination leads to a robust model with potential diagnostic value to discriminate the PD patients from matched controls. Methods The proposed translational approach was initiated by the analysis of secretomes from cells cultured under control or well-defined oxidative stress conditions, followed by the identification of proteins related to PD pathologic mechanisms that were altered between the two states. This pipeline was further translated into the analysis of undepleted plasma samples from 28 control and 31 PD patients. Results From the secretome analysis, several mitochondria-related proteins were found to be differentially released between control and stress conditions and to be able to distinguish the two secretomes. Similarly, two mitochondrial-related proteins were found to be significantly changed in a PD cohort compared to matched controls. Moreover, a linear discriminant model with potential diagnostic value to discriminate PD patients was obtained using the combination of these two proteins. Both proteins are associated with apoptotic mitochondrial changes, which may correspond to potential indicators of cell death. Moreover, one of these proteins, the VPS35 protein, was reported in plasma for the first time, and its quantification was only possible due to its previous identification in the secretome analysis. Conclusions In this work, an adaptation of a translational pipeline for biomarker selection was presented and transposed to neurological diseases, in the present case Parkinson’s Disease. The novelty and success of this pilot study may arise from the combination of: i) a translational research pipeline, where plasma samples are interrogated using knowledge previously obtained from the evaluation of cells’ secretome under oxidative stress; ii) the combined used of statistical analysis and an informed selection of candidates based on their link with relevant disease mechanisms, and iii) the use of SWATH-MS, an untargeted MS method that allows a complete record of the analyzed samples and a targeted data extraction of the quantitative values of proteins previously identified.http://link.springer.com/article/10.1186/s40035-020-00188-0Mitochondrial-related proteinsSWATH-MSParkinson’s diseaseBiomarker discoveryBlood-biomarkerSecretomes |
| spellingShingle | Sandra I. Anjo Patrícia Valério dos Santos Luiza Rosado Graça Baltazar Inês Baldeiras Diana Pires Andreia Gomes Cristina Januário Miguel Castelo-Branco Mário Grãos Bruno Manadas A different vision of translational research in biomarker discovery: a pilot study on circulatory mitochondrial proteins as Parkinson’s disease potential biomarkers Translational Neurodegeneration Mitochondrial-related proteins SWATH-MS Parkinson’s disease Biomarker discovery Blood-biomarker Secretomes |
| title | A different vision of translational research in biomarker discovery: a pilot study on circulatory mitochondrial proteins as Parkinson’s disease potential biomarkers |
| title_full | A different vision of translational research in biomarker discovery: a pilot study on circulatory mitochondrial proteins as Parkinson’s disease potential biomarkers |
| title_fullStr | A different vision of translational research in biomarker discovery: a pilot study on circulatory mitochondrial proteins as Parkinson’s disease potential biomarkers |
| title_full_unstemmed | A different vision of translational research in biomarker discovery: a pilot study on circulatory mitochondrial proteins as Parkinson’s disease potential biomarkers |
| title_short | A different vision of translational research in biomarker discovery: a pilot study on circulatory mitochondrial proteins as Parkinson’s disease potential biomarkers |
| title_sort | different vision of translational research in biomarker discovery a pilot study on circulatory mitochondrial proteins as parkinson s disease potential biomarkers |
| topic | Mitochondrial-related proteins SWATH-MS Parkinson’s disease Biomarker discovery Blood-biomarker Secretomes |
| url | http://link.springer.com/article/10.1186/s40035-020-00188-0 |
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