Posttranslational modifications of blood-derived alpha-synuclein as biochemical markers for Parkinson's disease

Hugo Vicente Miranda, Rafaela Cássio, Leonor Correia-Guedes, Marcos António Gomes, Ana Chegão, Elisa Miranda, Tiago Soares, Miguel Coelho, Mário Miguel Rosa, Joaquim J. Ferreira, Tiago Fleming Outeiro

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Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder known for the typical motor features associated. Pathologically, it is characterized by the intracellular accumulation of alpha-synuclein (aSyn) in Lewy bodies and Lewy neurites. Currently, there are no established biochemical markers for diagnosing or for following disease progression, a major limitation for the clinical practice. Posttranslational modifications (PTMs) in aSyn have been identified and implicated on its pathobiology. Since aSyn is abundant in blood erythrocytes, we aimed to evaluate whether PTMs of aSyn in the blood might hold value as a biomarker for PD. We examined 58 patients with PD and 30 healthy age-matched individuals. We found that the levels of Y125 phosphorylated, Y39 nitrated, and glycated aSyn were increased in PD, while those of SUMO were reduced. A combinatory analysis of the levels of these PTMs resulted in an increased sensitivity, with an area under curve (AUC) of 0.843 for PD versus healthy controls, and correlated with disease severity and duration. We conclude that the levels of these selected PTMs hold strong potential as biochemical markers for PD. Ultimately, our findings might facilitate the monitoring of disease progression in clinical trials, opening the possibility for developing more effective therapies against PD.

Original languageEnglish
Article number13713
Pages (from-to)Online
Number of pages11
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - 2017

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alpha-Synuclein
Post Translational Protein Processing
Parkinson Disease
Biomarkers
Disease Progression
Lewy Bodies
Neurites
Neurodegenerative Diseases
Area Under Curve
Erythrocytes
Clinical Trials

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Miranda, Hugo Vicente ; Cássio, Rafaela ; Correia-Guedes, Leonor ; Gomes, Marcos António ; Chegão, Ana ; Miranda, Elisa ; Soares, Tiago ; Coelho, Miguel ; Rosa, Mário Miguel ; Ferreira, Joaquim J. ; Outeiro, Tiago Fleming. / Posttranslational modifications of blood-derived alpha-synuclein as biochemical markers for Parkinson's disease. In: Scientific Reports. 2017 ; Vol. 7, No. 1. pp. Online.
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title = "Posttranslational modifications of blood-derived alpha-synuclein as biochemical markers for Parkinson's disease",
abstract = "Parkinson's disease (PD) is a progressive neurodegenerative disorder known for the typical motor features associated. Pathologically, it is characterized by the intracellular accumulation of alpha-synuclein (aSyn) in Lewy bodies and Lewy neurites. Currently, there are no established biochemical markers for diagnosing or for following disease progression, a major limitation for the clinical practice. Posttranslational modifications (PTMs) in aSyn have been identified and implicated on its pathobiology. Since aSyn is abundant in blood erythrocytes, we aimed to evaluate whether PTMs of aSyn in the blood might hold value as a biomarker for PD. We examined 58 patients with PD and 30 healthy age-matched individuals. We found that the levels of Y125 phosphorylated, Y39 nitrated, and glycated aSyn were increased in PD, while those of SUMO were reduced. A combinatory analysis of the levels of these PTMs resulted in an increased sensitivity, with an area under curve (AUC) of 0.843 for PD versus healthy controls, and correlated with disease severity and duration. We conclude that the levels of these selected PTMs hold strong potential as biochemical markers for PD. Ultimately, our findings might facilitate the monitoring of disease progression in clinical trials, opening the possibility for developing more effective therapies against PD.",
author = "Miranda, {Hugo Vicente} and Rafaela C{\'a}ssio and Leonor Correia-Guedes and Gomes, {Marcos Ant{\'o}nio} and Ana Cheg{\~a}o and Elisa Miranda and Tiago Soares and Miguel Coelho and Rosa, {M{\'a}rio Miguel} and Ferreira, {Joaquim J.} and Outeiro, {Tiago Fleming}",
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Miranda, HV, Cássio, R, Correia-Guedes, L, Gomes, MA, Chegão, A, Miranda, E, Soares, T, Coelho, M, Rosa, MM, Ferreira, JJ & Outeiro, TF 2017, 'Posttranslational modifications of blood-derived alpha-synuclein as biochemical markers for Parkinson's disease' Scientific Reports, vol. 7, no. 1, 13713, pp. Online. https://doi.org/10.1038/s41598-017-14175-5

Posttranslational modifications of blood-derived alpha-synuclein as biochemical markers for Parkinson's disease. / Miranda, Hugo Vicente; Cássio, Rafaela; Correia-Guedes, Leonor; Gomes, Marcos António; Chegão, Ana; Miranda, Elisa; Soares, Tiago; Coelho, Miguel; Rosa, Mário Miguel; Ferreira, Joaquim J.; Outeiro, Tiago Fleming.

In: Scientific Reports, Vol. 7, No. 1, 13713, 2017, p. Online.

Research output: Contribution to journalArticle

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T1 - Posttranslational modifications of blood-derived alpha-synuclein as biochemical markers for Parkinson's disease

AU - Miranda, Hugo Vicente

AU - Cássio, Rafaela

AU - Correia-Guedes, Leonor

AU - Gomes, Marcos António

AU - Chegão, Ana

AU - Miranda, Elisa

AU - Soares, Tiago

AU - Coelho, Miguel

AU - Rosa, Mário Miguel

AU - Ferreira, Joaquim J.

AU - Outeiro, Tiago Fleming

N1 - info:eu-repo/grantAgreement/FCT/3599-PPCDT/126579/PT# We are thankful to the patients and participants for their kind participation and donation of samples. This study was supported by Fundacao para a Ciencia e Tecnologia (FCT) EXPL/NEU-OSD/0606/2012, PTDC/NEUOSD/5644/2014. Authors were supported by: HVM (FCT, SFRH/BPD/64702/2009, SFRH/BPD/109347/2015); MG (FCT, EXPL/NEU-OSD/0606/2012); TFO (DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain-CNMPB).

PY - 2017

Y1 - 2017

N2 - Parkinson's disease (PD) is a progressive neurodegenerative disorder known for the typical motor features associated. Pathologically, it is characterized by the intracellular accumulation of alpha-synuclein (aSyn) in Lewy bodies and Lewy neurites. Currently, there are no established biochemical markers for diagnosing or for following disease progression, a major limitation for the clinical practice. Posttranslational modifications (PTMs) in aSyn have been identified and implicated on its pathobiology. Since aSyn is abundant in blood erythrocytes, we aimed to evaluate whether PTMs of aSyn in the blood might hold value as a biomarker for PD. We examined 58 patients with PD and 30 healthy age-matched individuals. We found that the levels of Y125 phosphorylated, Y39 nitrated, and glycated aSyn were increased in PD, while those of SUMO were reduced. A combinatory analysis of the levels of these PTMs resulted in an increased sensitivity, with an area under curve (AUC) of 0.843 for PD versus healthy controls, and correlated with disease severity and duration. We conclude that the levels of these selected PTMs hold strong potential as biochemical markers for PD. Ultimately, our findings might facilitate the monitoring of disease progression in clinical trials, opening the possibility for developing more effective therapies against PD.

AB - Parkinson's disease (PD) is a progressive neurodegenerative disorder known for the typical motor features associated. Pathologically, it is characterized by the intracellular accumulation of alpha-synuclein (aSyn) in Lewy bodies and Lewy neurites. Currently, there are no established biochemical markers for diagnosing or for following disease progression, a major limitation for the clinical practice. Posttranslational modifications (PTMs) in aSyn have been identified and implicated on its pathobiology. Since aSyn is abundant in blood erythrocytes, we aimed to evaluate whether PTMs of aSyn in the blood might hold value as a biomarker for PD. We examined 58 patients with PD and 30 healthy age-matched individuals. We found that the levels of Y125 phosphorylated, Y39 nitrated, and glycated aSyn were increased in PD, while those of SUMO were reduced. A combinatory analysis of the levels of these PTMs resulted in an increased sensitivity, with an area under curve (AUC) of 0.843 for PD versus healthy controls, and correlated with disease severity and duration. We conclude that the levels of these selected PTMs hold strong potential as biochemical markers for PD. Ultimately, our findings might facilitate the monitoring of disease progression in clinical trials, opening the possibility for developing more effective therapies against PD.

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