Protein nitration profile of CD3+ lymphocytes from Alzheimer disease patients: Novel hints on immunosenescence and biomarker detection

Federica Iavarone, Massimo Castagnola, Antonella Tramutola, Giulia Abate, Chiara Lanzillotta, Francesca Triani, Eugenio Barone, Mariagrazia Marziano, Maurizio Memo, Emirena Garrafa, D. Allan Butterfield, Marzia Perluigi, Fabio Di Domenico, Daniela Uberti

Risultato della ricerca: Contributo in rivistaArticolo in rivista

14 Citazioni (Scopus)

Abstract

Alzheimer's disease (AD) is a progressive form of dementia characterized by increased production of amyloid-β plaques and hyperphosphorylated tau protein, mitochondrial dysfunction, elevated oxidative stress, reduced protein clearance, among other. Several studies showed systemic modifications of immune and inflammatory systems due, in part, to decreased levels of CD3+ lymphocytes in peripheral blood in AD. Considering that oxidative stress, both in the brain and in the periphery, can influence the activation and differentiation of T-cells, we investigated the 3-nitrotyrosine (3-NT) proteome of blood T-cells derived from AD patients compared to non-demented (ND) subjects by using a proteomic approach. 3-NT is a formal protein oxidation and index of nitrosative stress. We identified ten proteins showing increasing levels of 3-NT in CD3+ T-cells from AD patients compared with ND subjects. These proteins are involved in energy metabolism, cytoskeletal structure, intracellular signaling, protein folding and turnover, and antioxidant response and provide new insights into the molecular mechanism that impact reduced T-cell differentiation in AD. Our results highlight the role of peripheral oxidative stress in T-cells related to immune-senescence during AD pathology focusing on the specific targets of protein nitration that conceivably can be suitable to further therapies. Further, our data demonstrate common targets of protein nitration between the brain and the periphery, supporting their significance as disease biomarkers.
Lingua originaleEnglish
pagine (da-a)430-439
Numero di pagine10
RivistaFREE RADICAL BIOLOGY & MEDICINE
Volume129
DOI
Stato di pubblicazionePubblicato - 2018

Keywords

  • +
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease
  • Alzheimer's disease
  • Antioxidants
  • Biomarkers
  • CD3
  • CD3 Complex
  • Case-Control Studies
  • Cell Separation
  • Cytoskeletal Proteins
  • Energy Metabolism
  • Female
  • Gene Expression
  • Humans
  • Immunesenescence
  • Lymphocytes
  • Male
  • Middle Aged
  • Nitro Compounds
  • Nitrosative Stress
  • Oxidative Stress
  • Oxidative stress
  • Primary Cell Culture
  • Protein nitration
  • Proteome
  • Proteomics
  • Signal Transduction
  • Tyrosine
  • lymphocytes

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