Objective To perform a rigorous in-depth proteomics analysis to identify circulating biomarker signatures for idiopathic REM sleep behavior disorder (RBD), capable of providing new insights into the underlying pathogenic mechanisms and putative α-synuclein-related neurodegenerative processes. Methods Serum samples from patients with idiopathic RBD (n = 9) and healthy controls (n = 10) were subjected to a thorough liquid chromatography–mass spectrometry (MS)/MS proteomics analysis using ultimate 3,000 nanoLC interfaced to an ESI-orbitrap velos. Data were analyzed with a systems biology approach to identify altered pathways in RBD. Results We identified 259 proteins, 11 of which displayed significantly altered expression level in patients with RBD as compared to controls. Significant reduction in serum levels of dopamine β-hydroxylase (DBH) and vitamin D binding protein (GC) were consistent with alterations in the norepinephrinergic (NErgic) and dopaminergic systems, respectively. Additional altered protein profiles indicated that immunity, inflammation, complement, and coagulation also play a role in RBD pathophysiology. Conclusions Our results shed light on the protein signature profile, molecular pathways, and mechanisms involved in the pathogenesis of RBD and its clinical manifestation. This knowledge opens a new avenue towards more accurate and timely diagnosis and characterization of RBD, which might ultimately translate into new therapeutic strategies with disease-modifying effects. Further evaluation of the identified markers is required to confirm their diagnostic value and potential to guide clinical decision-making.

Novel biomarker signatures for idiopathic REM sleep behavior disorder: A proteomic and system biology approach

Mondello, Stefania
Primo
Conceptualization
;
2018-01-01

Abstract

Objective To perform a rigorous in-depth proteomics analysis to identify circulating biomarker signatures for idiopathic REM sleep behavior disorder (RBD), capable of providing new insights into the underlying pathogenic mechanisms and putative α-synuclein-related neurodegenerative processes. Methods Serum samples from patients with idiopathic RBD (n = 9) and healthy controls (n = 10) were subjected to a thorough liquid chromatography–mass spectrometry (MS)/MS proteomics analysis using ultimate 3,000 nanoLC interfaced to an ESI-orbitrap velos. Data were analyzed with a systems biology approach to identify altered pathways in RBD. Results We identified 259 proteins, 11 of which displayed significantly altered expression level in patients with RBD as compared to controls. Significant reduction in serum levels of dopamine β-hydroxylase (DBH) and vitamin D binding protein (GC) were consistent with alterations in the norepinephrinergic (NErgic) and dopaminergic systems, respectively. Additional altered protein profiles indicated that immunity, inflammation, complement, and coagulation also play a role in RBD pathophysiology. Conclusions Our results shed light on the protein signature profile, molecular pathways, and mechanisms involved in the pathogenesis of RBD and its clinical manifestation. This knowledge opens a new avenue towards more accurate and timely diagnosis and characterization of RBD, which might ultimately translate into new therapeutic strategies with disease-modifying effects. Further evaluation of the identified markers is required to confirm their diagnostic value and potential to guide clinical decision-making.
2018
File in questo prodotto:
File Dimensione Formato  
2018 Neurology Mond.pdf

solo utenti autorizzati

Descrizione: Edizione online
Tipologia: Versione Editoriale (PDF)
Licenza: Tutti i diritti riservati (All rights reserved)
Dimensione 885.06 kB
Formato Adobe PDF
885.06 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Novel biomarker.pdf

solo utenti autorizzati

Descrizione: Articolo principale. Edizione a stampa (2018)
Tipologia: Versione Editoriale (PDF)
Licenza: Tutti i diritti riservati (All rights reserved)
Dimensione 826.76 kB
Formato Adobe PDF
826.76 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Erratum_Mondello_Novel_Biomarker.pdf

solo utenti autorizzati

Descrizione: Erratum: 2018;91:1117. doi:10.1212/WNL.0000000000006791
Tipologia: Altro materiale allegato (es. Copertina, Indice, Materiale supplementare, Brevetti, Spin off, Start up, etc.)
Licenza: Altra licenza (allegare)
Dimensione 107.05 kB
Formato Adobe PDF
107.05 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11570/3131343
Citazioni
  • ???jsp.display-item.citation.pmc??? 14
  • Scopus 26
  • ???jsp.display-item.citation.isi??? 24
social impact