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Top-Down Proteomics of Human Saliva Highlights Anti-inflammatory, Antioxidant, and Antimicrobial Defense Responses in Alzheimer Disease.

Frontiers in neuroscience | 2021

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.

Pubmed ID: 34121996 RIS Download

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This is a list of tools and resources that we have found mentioned in this publication.


Proteomics Identifications (PRIDE) (tool)

RRID:SCR_003411

Centralized, standards compliant, public data repository for proteomics data, including protein and peptide identifications, post-translational modifications and supporting spectral evidence. Originally it was developed to provide a common data exchange format and repository to support proteomics literature publications. This remit has grown with PRIDE, with the hope that PRIDE will provide a reference set of tissue-based identifications for use by the community. The future development of PRIDE has become closely linked to HUPO PSI. PRIDE encourages and welcomes direct user submissions of protein and peptide identification data to be published in peer-reviewed publications. Users may Browse public datasets, use PRIDE BioMart for custom queries, or download the data directly from the FTP site. PRIDE has been developed through a collaboration of the EMBL-EBI, Ghent University in Belgium, and the University of Manchester.

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ProteomeXchange (tool)

RRID:SCR_004055

A data repository for proteomic data sets. The ProteomeExchange consortium, as a whole, aims to provide a coordinated submission of MS proteomics data to the main existing proteomics repositories, as well as to encourage optimal data dissemination. ProteomeXchange provides access to a number of public databases, and users can access and submit data sets to the consortium's PRIDE database and PASSEL/PeptideAtlas.

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UniProtKB (tool)

RRID:SCR_004426

Central repository for collection of functional information on proteins, with accurate and consistent annotation. In addition to capturing core data mandatory for each UniProtKB entry (mainly, the amino acid sequence, protein name or description, taxonomic data and citation information), as much annotation information as possible is added. This includes widely accepted biological ontologies, classifications and cross-references, and experimental and computational data. The UniProt Knowledgebase consists of two sections, UniProtKB/Swiss-Prot and UniProtKB/TrEMBL. UniProtKB/Swiss-Prot (reviewed) is a high quality manually annotated and non-redundant protein sequence database which brings together experimental results, computed features, and scientific conclusions. UniProtKB/TrEMBL (unreviewed) contains protein sequences associated with computationally generated annotation and large-scale functional characterization that await full manual annotation. Users may browse by taxonomy, keyword, gene ontology, enzyme class or pathway.

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Sigma-Aldrich (tool)

RRID:SCR_008988

American chemical, life science and biotechnology company owned by Merck KGaA. Merger of Sigma Chemical Company and Aldrich Chemical Company. Provides organic and inorganic chemicals, building blocks, reagents, advanced materials and stable isotopes for chemical synthesis, medicinal chemistry and materials science, antibiotics, buffers, carbohydrates, enzymes, forensic tools, hematology and histology, nucleotides, proteins, peptides, amino acids and their derivatives.

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Program to Reduce Incontinence by Diet and Exercise (tool)

RRID:SCR_009018

Randomized controlled trial being conducted at two clinical centers in the United States to learn more about the effects of weight loss on urinary incontinence. About 330 overweight women aged 30 or older will participate and will be followed for 18 months. Efficacy of weight reduction as a treatment for urinary incontinence will be examined at 6 months following the intensive weight control program, and the sustained impact of the intervention will be examined at 18 months. To increase the maintenance of weight reduction and facilitate evaluation of the enduring impact of weight loss on urinary incontinence, they propose to study a motivation-based weight maintenance program. At the end of the intensive weight control program, women randomized to the weight loss program will be randomized to either a 12-month skill-based maintenance intervention or to a motivation-based maintenance intervention. The maintenance interventions maximize the potential for sustained weight loss and will allow them to determine if long-term weight reduction will produce continued improvement in urinary incontinence.

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ExPASy Bioinformatics Resource Portal (tool)

RRID:SCR_012880

Portal which provides access to scientific databases and software tools (i.e., resources) in different areas of life sciences including proteomics, genomics, phylogeny, systems biology, population genetics, transcriptomics etc. It contains resources from many different SIB groups as well as external institutions.

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Protein Prospector (tool)

RRID:SCR_014558

A package of over twenty mass spectrometry-based tools primarily geared toward proteomic data analysis and database mining. It can be run from the command line, but is primarily used through a web browser, and there is a public website that allows anyone to use the software without local installation. Tandem mass spectrometry analysis tools are used for database searching and identification of peptides, including post-translationally modified peptides and cross-linked peptides. Support for isotope and label-free quantification from this type of data is provided. MS-Viewer software allows sharing and displaying of annotated spectra from many different tandem mass spectrometry data analysis packages. Other tools include software for analyzing peptide mass fingerprinting data (MS-Fit); prediction of theoretical fragmentation of peptides (MS-Product); theoretical chemical or enzymatic digestion of proteins (MS-Digest); and theoretical modeling of the isotope distribution of any chemical, including peptides (MS-Isotope). Searches using amino acid sequence can be used to identify homologous peptides in a database (MS-Pattern); the use of the combination of amino acid sequence and masses can be used for homologous peptide and protein identification using MS-Homology. Tandem mass spectrometry peak list files can be filtered for the presence of certain peaks or neutral losses using MS-Filter. Given a list of proteins, MS-Bridge can report all potential cross-linked peptide combinations of a specified mass. Given a precursor peptide mass and information about known amino acid presence, absence, or modifications, MS-Comp can report all amino acid combinations that could lead to the observed mass.

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Thermo Xcalibur (tool)

RRID:SCR_014593

A software which acquires and processes data sets, primarily through the Xcalibur system.

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