TY - JOUR
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.
UR - http://www.scopus.com/inward/record.url?scp=85032025050&partnerID=8YFLogxK
U2 - 10.1038/s41598-017-14175-5
DO - 10.1038/s41598-017-14175-5
M3 - Article
C2 - 29057912
AN - SCOPUS:85032025050
SN - 2045-2322
VL - 7
SP - Online
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 13713
ER -