期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 129, 期 -, 页码 430-439出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2018.10.414
关键词
Alzheimer's disease; Protein nitration; CD3(+) lymphocytes; Oxidative stress; Immunesenescence; Proteomics
资金
- Ministry of Instruction, Universities and Research (MIUR), Italy [RBSI144MT]
- Sapienza University of Rome, Italy [C26H15JT9X, RG116154C9214D1A]
- People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007-2013) [624341]
- Banca d'Italia, Italy [12868/17]
- Fondazione Cariplo, Italy [2014-0769]
- University of Brescia, Italy
Alzheimer's disease (AD) is a progressive form of dementia characterized by increased production of amyloid-beta 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.
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