TY - JOUR
T1 - Characterization of Cystatin B Interactome in Saliva from Healthy Elderly and Alzheimer’s Disease Patients
AU - Contini, Cristina
AU - Serrao, Simone
AU - Manconi, Barbara
AU - Olianas, Alessandra
AU - Iavarone, Federica
AU - Guadalupi, Giulia
AU - Messana, Irene
AU - Castagnola, Massimo
AU - Masullo, Carlo
AU - Bizzarro, Alessandra
AU - Turck, Christoph W.
AU - Maccarrone, Giuseppina
AU - Cabras, Tiziana
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - affinity purification
KW - alzheimer’s disease
KW - bottom-up proteomics
KW - cystatin B
KW - interactome
KW - mass spectrometry
KW - saliva
KW - affinity purification
KW - alzheimer’s disease
KW - bottom-up proteomics
KW - cystatin B
KW - interactome
KW - mass spectrometry
KW - saliva
UR - http://hdl.handle.net/10807/262263
U2 - 10.3390/life13030748
DO - 10.3390/life13030748
M3 - Article
SN - 2075-1729
VL - 13
SP - N/A-N/A
JO - Life
JF - Life
ER -