Dataset Information

Characterization of novel human cystatin B salivary interactome in Alzheimer’s disease and healthy subjects.

ABSTRACT: Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease in the elderly, characterized by the accumulation in the brain of misfolded proteins, inflammation, and oxidative damage leading to neuronal cell death. The necessity of searching for new non-invasive biomarkers in tissues or body fluids easy and painless to collect has been evidenced. In this context, saliva has been chosen to investigate new possible biomarkers using a proteomics-based approach. Previous results obtained on the acid-soluble fraction of saliva from AD patients by a Top-Down proteomic approach revealed the potential role of cystatin B in the disease, a protein capable of interacting with other proteins, including amyloid beta, and to homo-polymerize. Thus, the first aim of the present project has been to demonstrate the existence of a multiprotein complex with cystatin B in whole saliva samples and to characterize it, secondly, we further studied the cystatin B interactome to individuate any qualitative-quantitative difference between AD patients and healthy subjects age and sex matched. To these aims, we performed some preliminary tests mainly by western blot to look for high molecular weight positive signals related to cystatin B in saliva, and, then, in order to characterize the presence of potential multiprotein complexes, we performed Co-IP assays followed by in gel tryptic digestion and RP-nanoHPLC-HR-ESI-MS/MS analysis (reverse-phase nano-high-performance liquid chromatography separation coupled to electrospray-ion trap tandem mass spectrometry).

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Saliva

DISEASE(S): Alzheimer's Disease

SUBMITTER: Cristina Contini

LAB HEAD: Tiziana Cabras

PROVIDER: PXD039286 | Pride | 2023-05-10

REPOSITORIES: Pride

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Publications

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

Contini Cristina C Serrao Simone S Manconi Barbara B Olianas Alessandra A Iavarone Federica F Guadalupi Giulia G Messana Irene I Castagnola Massimo M Masullo Carlo C Bizzarro Alessandra A Turck Christoph W CW Maccarrone Giuseppina G Cabras Tiziana T

Life (Basel, Switzerland) 20230310 3

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 pat ...[more]

PMID: 36983903

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Project description:Malaria is by far the world’s most significant tropical infectious disease and over the last a few decades large-scale malaria epidemics have happened in almost all continents. Plasmodium falciparum and Plasmodium vivax account for over 90% of the total malaria cases worldwide. The estimated number of annual clinical cases of vivax malaria is even higher than that of falciparum malaria, but yet the morbidity associated with this infection and its spectrum of disease is largely neglected. Identification of serum/plasma proteins, which exhibit altered abundance at the onset and during the acute phase of any infection, could be informative to understand the pathobiology of different infectious diseases and host responses against the invading pathogens. To this end, in recent years, quite a few research groups including us have investigated alterations in serum/plasma proteome in severe and non-severe falciparum malaria (and also vivax malaria) to study malaria pathogenesis. In all these studies, serum/plasma proteome of the malaria patients have been analyzed during the febrile stages of the infection, either at the onset of the disease or at the fastigium stage. However, temporal profiling of serum/plasma proteome during acute and remission stages in malaria, which can provide snapshots of the transient and enduring alterations in serum proteome during the febrile, defervescence and convalescent stages has not been reported hitherto. Here, we report, for the first time, serum proteomic alterations in a longitudinal cohort of P. vivax infected patients to elucidate host responses when fever is established (temperature of the body reaches above higher normal level), during the stage when the temperature comes down to normal, and also during the gradual recovery of health after the illness. The three stages discussed in our study have been categorically chosen depending upon the clinical course of uncomplicated vivax malaria. Analysis of the early febrile stage represents host proteome profile immediately after onset of the infection, without any effect of anti-malarial drugs. The second, defervescence stage, reflects any immediate change in blood proteome at early recovery phase, while the convalescent stage indicates a phase after administration of 14 days radical cure treatment with primaquine and a complete recovery, when none of the patients displayed any apparent symptoms of malaria. We have also performed an extensive quantitative proteomics analysis to compare the serum proteome profiles of vivax malaria patients with low and moderately-high parasitemia with healthy community controls. Isobaric tags for relative and absolute quantitation (iTRAQ) and 2-D fluorescence difference gel electrophoresis (2D-DIGE)-based quantitative proteomics approaches were used in the discovery-phase of the study, and some selected differentially abundant serum proteins were validated further by using ELISA. Interestingly, some of the serum proteins like Serum amyloid A, Apolipoprotein A1, C-reactive protein, Titin and Haptoglobin, were found to be sequentially altered with respect to increased parasite counts, while many of the quantified candidates such as Hemopexin, Vitronectin, Clusterin and Apolipoprotein E exhibited nearly equal levels of differential serum abundance in different parasitemic malaria patients. Analysis of a longitudinal cohort of malaria patients indicated reversible alterations in serum levels of some proteins such as Haptoglobin, Apolipoprotein E, Apolipoprotein A1, Carbonic anhydrase 1, and Hemoglobin subunit alpha upon treatment; however, the levels of a few other proteins did not return to the baseline even during the convalescent phase of the infection. Identification of the differentially abundant serum proteins and associated physiological pathways in vivax malaria along with phase-specific protein profiles during the acute and convalescent phases of the infection can effectively enhance our understanding of P. vivax disease biology and host immune responses.

Dataset Information

Characterization of novel human cystatin B salivary interactome in Alzheimer’s disease and healthy subjects.

Publications

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

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