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.

Details

Title
Posttranslational modifications of blood-derived alpha-synuclein as biochemical markers for Parkinson’s disease
Author
Hugo Vicente Miranda 1   VIAFID ORCID Logo  ; Cássio, Rafaela 2 ; Correia-Guedes, Leonor 3 ; Gomes, Marcos António 2   VIAFID ORCID Logo  ; Chegão, Ana 4 ; Miranda, Elisa 5 ; Soares, Tiago 5 ; Coelho, Miguel 3 ; Mário Miguel Rosa 3 ; Ferreira, Joaquim J 5 ; Tiago Fleming Outeiro 6 

1  CEDOC, Chronic Diseases Research Centre, NOVA Medical School|Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Campo dos Mártires da Pátria, 130, Lisboa, Portugal; Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal 
2  Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal 
3  Clinical Pharmacology Unit, Instituto de Medicina Molecular, Lisbon, Portugal; Department of Neurosciences and Mental Health, Neurology, Hospital de Santa Maria-CHLN, Lisbon, Portugal 
4  CEDOC, Chronic Diseases Research Centre, NOVA Medical School|Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Campo dos Mártires da Pátria, 130, Lisboa, Portugal 
5  Clinical Pharmacology Unit, Instituto de Medicina Molecular, Lisbon, Portugal 
6  CEDOC, Chronic Diseases Research Centre, NOVA Medical School|Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Campo dos Mártires da Pátria, 130, Lisboa, Portugal; Department of Experimental Neurodegeneration, Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Center for Biostructural Imaging of Neurodegeneration, University Medical Center Göttingen, Waldweg 33, Göttingen, Germany; Max Planck Institute for Experimental Medicine, Göttingen, Germany 
Pages
1-11
Publication year
2017
Publication date
Oct 2017
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41598-017-14175-5
ProQuest document ID
2123042621
Copyright
© 2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.