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pmid:36983903

Characterization of Cystatin B Interactome in Saliva from Healthy Elderly and Alzheimer's Disease Patients.

Cristina Contini · Simone Serrao · Barbara Manconi · Alessandra Olianas · Federica Iavarone · Giulia Guadalupi · Irene Messana · Massimo Castagnola · Carlo Masullo · Alessandra Bizzarro · Christoph W Turck · Giuseppina Maccarrone · Tiziana Cabras

Life (Basel, Switzerland) · 2023 doi:10.3390/life13030748

Paper

complete

Experiment

partial

Data

partial

Analysis

partial

Execution

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title
Characterization of Cystatin B Interactome in Saliva from Healthy Elderly and Alzheimer's Disease Patients.
doi
10.3390/life13030748
pmid
36983903
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[0]
Cristina Contini
[1]
Simone Serrao
[2]
Barbara Manconi
[3]
Alessandra Olianas
[4]
Federica Iavarone
[5]
Giulia Guadalupi
[6]
Irene Messana
[7]
Massimo Castagnola
[8]
Carlo Masullo
[9]
Alessandra Bizzarro
[10]
Christoph W Turck
[11]
Giuseppina Maccarrone
[12]
Tiziana Cabras
journal
Life (Basel, Switzerland)
year
2023
abstract
Cystatin B is a small, multifunctional protein involved in the regulation of inflammation, innate immune response, and neuronal protection and found highly abundant in the brains of patients with Alzheimer's disease (AD). Recently, our study demonstrated a significant association between the level of salivary cystatin B and AD. Since the protein is able to establish protein-protein interaction (PPI) in different contexts and aggregation-prone proteins and the PPI networks are relevant for AD pathogenesis, and due to the relevance of finding new AD markers in peripheral biofluids, we thought it was interesting to study the possible involvement of cystatin B in PPIs in saliva and to evaluate differences and similarities between AD and age-matched elderly healthy controls (HC). For this purpose, we applied a co-immunoprecipitation procedure and a bottom-up proteomics analysis to purify, identify, and quantify cystatin B interactors. Results demonstrated for the first time the existence of a salivary cystatin B-linked multi-protein complex composed by 82 interactors and largely expressed in the body. Interactors are involved in neutrophil activation, antimicrobial activity, modulation of the cytoskeleton and extra-cellular matrix (ECM), and glucose metabolism. Preliminary quantitative data showed significantly lower levels of triosophosphate isomerase 1 and higher levels of mucin 7, BPI, and matrix Gla protein in AD with respect to HC, suggesting implications associated with AD of altered glucose metabolism, antibacterial activities, and calcification-associated processes. Data are available via ProteomeXchange with identifiers PXD039286 and PXD030679.
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Therefore, the comparison between AD or HC proteins’ LFQ abundances was carried out with the two-sample student t-test, and the differences were considered significant when the p value was less than 0.05 and the fold change was above ±1.0 with 250 randomizations.
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Preliminary quantitative data showed significantly lower levels of triosophosphate isomerase 1 and higher levels of mucin 7, BPI, and matrix Gla protein in AD with respect to HC, suggesting implications associated with AD of altered glucose metabolism, antibacterial activities, and calcification-associated processes.
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Preliminary quantitative data showed significantly lower levels of triosophosphate isomerase 1 and higher levels of mucin 7, BPI, and matrix Gla protein in AD with respect to HC, suggesting implications associated with AD of altered glucose metabolism, antibacterial activities, and calcification-associated processes.
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Characterization of novel human cystatin B salivary interactome in Alzheimer’s disease and healthy subjects.
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Recently, our study demonstrated a significant association between the level of salivary cystatin B and AD. Since the protein is able to establish protein-protein interaction (PPI) in different contexts and aggregation-prone proteins and the PPI networks are relevant for AD pathogenesis, and due to the relevance of finding new AD markers in peripheral biofluids, we thought it was interesting to study the possible involvement of cystatin B in PPIs in saliva and to evaluate differences and similarities between AD and age-matched elderly healthy controls (HC). For this purpose, we applied a co-immunoprecipitation procedure and a bottom-up proteomics analysis to purify, identify, and quantify cystatin B interactors. Results demonstrated for the first time the existence of a salivary cystatin B-linked multi-protein complex composed by 82 interactors and largely expressed in the body. Interactors are involved in neutrophil activation, antimicrobial activity, modulation of the cytoskeleton and extra-cellular matrix (ECM), and glucose metabolism. Preliminary quantitative data showed significantly lower levels of triosophosphate isomerase 1 and higher levels of mucin 7, BPI, and matrix Gla protein in AD with respect to HC, suggesting implications associated with AD of altered glucose metabolism, antibacterial activities, and calcification-associated processes. Data are available via ProteomeXchange with identifiers PXD039286 and PXD030679.", "claims": [{"id": "claim-method", "statement": "Therefore, the comparison between AD or HC proteins’ LFQ abundances was carried out with the two-sample student t-test, and the differences were considered significant when the p value was less than 0.05 and the fold change was above ±1.0 with 250 randomizations.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36983903", "locator": "sections[9] \"2.7. 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