A top-down proteomic approach reveals a salivary protein profile able to classify Parkinson's disease with respect to Alzheimer's disease patients and to healthy controls.

Alzheimer's disease Parkinson's disease S100A9 cystatins salivary proteomics

Journal

Proteomics
ISSN: 1615-9861
Titre abrégé: Proteomics
Pays: Germany
ID NLM: 101092707

Informations de publication

Date de publication:
04 Aug 2023
Historique:
revised: 25 07 2023
received: 29 04 2023
accepted: 26 07 2023
medline: 5 8 2023
pubmed: 5 8 2023
entrez: 4 8 2023
Statut: aheadofprint

Résumé

Parkinson's disease (PD) is a complex neurodegenerative disease with motor and non-motor symptoms. Diagnosis is complicated by lack of reliable biomarkers. To individuate peptides and/or proteins with diagnostic potential for early diagnosis, severity and discrimination from similar pathologies, the salivary proteome in 36 PD patients was investigated in comparison with 36 healthy controls (HC) and 35 Alzheimer's disease (AD) patients. A top-down platform based on HPLC-ESI-IT-MS allowed characterizing and quantifying intact peptides, small proteins and their PTMs (overall 51). The three groups showed significantly different protein profiles, PD showed the highest levels of cystatin SA and antileukoproteinase and the lowest of cystatin SN and some statherin proteoforms. HC exhibited the lowest abundance of thymosin β4, short S100A9, cystatin A, and dimeric cystatin B. AD patients showed the highest abundance of α-defensins and short oxidized S100A9. Moreover, different proteoforms of the same protein, as S-cysteinylated and S-glutathionylated cystatin B, showed opposite trends in the two pathological groups. Statherin, cystatins SA and SN classified accurately PD from HC and AD subjects. α-defensins, histatin 1, oxidized S100A9, and P-B fragments were the best classifying factors between PD and AD patients. Interestingly statherin and thymosin β4 correlated with defective olfactory functions in PD patients. All these outcomes highlighted implications of specific proteoforms involved in the innate-immune response and inflammation regulation at oral and systemic level, suggesting a possible panel of molecular and clinical markers suitable to recognize subjects affected by PD.

Identifiants

pubmed: 37541286
doi: 10.1002/pmic.202300202
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e2300202

Subventions

Organisme : FIR 2019 Alessandra Olianas
Organisme : FIR-2019 and FIR 2020 Cabras Tiziana from University of Cagliari

Informations de copyright

© 2023 The Authors. Proteomics published by Wiley-VCH GmbH.

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Auteurs

Cristina Contini (C)

Department of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria Monserrato, Monserrato, CA, Italy.

Laura Fadda (L)

Department of Medical Sciences and Public Health, Institute of Neurology, Cagliari, Italy.

Greca Lai (G)

Department of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria Monserrato, Monserrato, CA, Italy.

Carla Masala (C)

Department of Biomedical Sciences University of Cagliari, Cittadella Univ. Monserrato, Monserrato, Italy.

Alessandra Olianas (A)

Department of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria Monserrato, Monserrato, CA, Italy.

Massimo Castagnola (M)

Proteomics Laboratory. European Center for Brain Research, (IRCCS) Santa Lucia Foundation, Rome, Italy.

Irene Messana (I)

Consiglio Nazionale delle Ricerche, Istituto di Scienze e Tecnologie Chimiche "Giulio Natta", Rome, Italy.

Federica Iavarone (F)

Department of Basic Biotechnological Sciences, Intensive and Perioperative Clinics, Rome, Italy.
Fondazione Policlinico Universitario "A. Gemelli", IRCCS, Rome, Italy.

Alessandra Bizzarro (A)

Fondazione Policlinico Universitario "A. Gemelli", IRCCS, Rome, Italy.
Department of Geriatrics, Orthopaedics and Rheumatology, Rome, Italy.

Carlo Masullo (C)

Department of Neuroscience, Neurology Section, Università Cattolica del Sacro Cuore Rome, Rome, Italy.

Paolo Solla (P)

Neurological Unit, Department of Medicine, Surgery and Pharmacy, University of Sassari, Sassari, Italy.

Giovanni Defazio (G)

Department of Medical Sciences and Public Health, Institute of Neurology, Cagliari, Italy.

Barbara Manconi (B)

Department of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria Monserrato, Monserrato, CA, Italy.

Giacomo Diaz (G)

Department of Biomedical Sciences University of Cagliari, Cittadella Univ. Monserrato, Monserrato, Italy.

Tiziana Cabras (T)

Department of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria Monserrato, Monserrato, CA, Italy.

Classifications MeSH