TY - JOUR
T1 - Top-Down Proteomics of Human Saliva Highlights Anti-inflammatory, Antioxidant, and Antimicrobial Defense Responses in Alzheimer Disease
AU - Contini, Cristina
AU - Olianas, Alessandra
AU - Serrao, Simone
AU - Deriu, Carla
AU - Iavarone, Federica
AU - Boroumand, Mozhgan
AU - Bizzarro, Alessandra
AU - Lauria, Alessandra
AU - Faa, Gavino
AU - Castagnola, Massimo
AU - Messana, Irene
AU - Manconi, Barbara
AU - Masullo, Carlo
AU - Cabras, Tiziana
N1 - Funding Information:
We thank Enzo Tramontano (Department of Life and Environmental Sciences of University of Cagliari) for letting us use the ChemiDoc MP Imaging System (Bio-Rad). Funding. This study was supported by funds from Cagliari University (FIR-2019 Cabras Tiziana, FIR-2019 Olianas Alessandra, FIR-2019 Manconi Barbara).
Publisher Copyright:
© Copyright © 2021 Contini, Olianas, Serrao, Deriu, Iavarone, Boroumand, Bizzarro, Lauria, Faa, Castagnola, Messana, Manconi, Masullo and Cabras.
PY - 2021/5/26
Y1 - 2021/5/26
N2 - Alzheimer disease (AD) is the most prevalent neurodegenerative disease in the elderly, characterized by accumulation in the brain of misfolded proteins, inflammation, and oxidative damage leading to neuronal cell death. By considering the viewpoint that AD onset and worsening may be influenced by environmental factors causing infection, oxidative stress, and inflammatory reaction, we investigated the changes of the salivary proteome in a population of patients with respect to that in healthy controls (HCs). Indeed, the possible use of saliva as a diagnostic tool has been explored in several oral and systemic diseases. Moreover, the oral cavity continuously established adaptative and protective processes toward exogenous stimuli. In the present study, qualitative/quantitative variations of 56 salivary proteoforms, including post-translationally modified derivatives, have been analyzed by RP-HPLC-ESI-IT-MS and MS/MS analyses, and immunological methods were applied to validate MS results. The salivary protein profile of AD patients was characterized by significantly higher levels of some multifaceted proteins and peptides that were either specific to the oral cavity or also expressed in other body districts: (i) peptides involved in the homeostasis of the oral cavity; (ii) proteins acting as ROS/RNS scavengers and with a neuroprotective role, such as S100A8, S100A9, and their glutathionylated and nitrosylated proteoforms; cystatin B and glutathionylated and dimeric derivatives; (iii) proteins with antimicrobial activity, such as α-defensins, cystatins A and B, histatin 1, statherin, and thymosin β4, this last with a neuroprotective role at the level of microglia. These results suggested that, in response to injured conditions, Alzheimer patients established defensive mechanisms detectable at the oral level. Data are available via ProteomeXchange with identifier PXD021538.
AB - Alzheimer disease (AD) is the most prevalent neurodegenerative disease in the elderly, characterized by accumulation in the brain of misfolded proteins, inflammation, and oxidative damage leading to neuronal cell death. By considering the viewpoint that AD onset and worsening may be influenced by environmental factors causing infection, oxidative stress, and inflammatory reaction, we investigated the changes of the salivary proteome in a population of patients with respect to that in healthy controls (HCs). Indeed, the possible use of saliva as a diagnostic tool has been explored in several oral and systemic diseases. Moreover, the oral cavity continuously established adaptative and protective processes toward exogenous stimuli. In the present study, qualitative/quantitative variations of 56 salivary proteoforms, including post-translationally modified derivatives, have been analyzed by RP-HPLC-ESI-IT-MS and MS/MS analyses, and immunological methods were applied to validate MS results. The salivary protein profile of AD patients was characterized by significantly higher levels of some multifaceted proteins and peptides that were either specific to the oral cavity or also expressed in other body districts: (i) peptides involved in the homeostasis of the oral cavity; (ii) proteins acting as ROS/RNS scavengers and with a neuroprotective role, such as S100A8, S100A9, and their glutathionylated and nitrosylated proteoforms; cystatin B and glutathionylated and dimeric derivatives; (iii) proteins with antimicrobial activity, such as α-defensins, cystatins A and B, histatin 1, statherin, and thymosin β4, this last with a neuroprotective role at the level of microglia. These results suggested that, in response to injured conditions, Alzheimer patients established defensive mechanisms detectable at the oral level. Data are available via ProteomeXchange with identifier PXD021538.
KW - Alzheimer disease
KW - antimicrobial peptides
KW - cystatins
KW - oxidative stress
KW - S100A
KW - salivary proteomics
KW - thymosin β4
KW - α-defensins
UR - http://www.scopus.com/inward/record.url?scp=85107689076&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85107689076&partnerID=8YFLogxK
U2 - 10.3389/fnins.2021.668852
DO - 10.3389/fnins.2021.668852
M3 - Article
AN - SCOPUS:85107689076
VL - 15
JO - Frontiers in Neuroscience
JF - Frontiers in Neuroscience
SN - 1662-4548
M1 - 668852
ER -