Narodowe Centrum Nauki
Description: Prader-Willi syndrome (PWS) is a genetic disorder first described in 1956 by three Swiss
physicians: Prader, Labhart, and Willi. The cause of PWS is a disruption in the expression of certain
paternal genes located on chromosome 15, specifically in the 15q11.2-13 region, most commonly in the
form of deletion of the paternal copy or maternal uniparental disomy [1]. Infants suffering from PWS
exhibit delayed development, hypotonia, and lack of appetite [2],[3]. In later stages of life, a disrupted
sense of satiety (hyperphagia) and other symptoms related to hypothalamic dysfunction, such as
intellectual disability, thermoregulation disorders, and increased pain threshold, emerge [2],[3].
Importantly, patients with PWS show several symptoms in the oral cavity, including hypoplastic enamel,
dental caries, and periodontal disease [2]–[4]. One possible cause may be reduced secretion of abnormal
saliva, which is dense, sticky, viscous, and more acidic [2]–[4]. Consequently, important protective and
antibacterial functions of saliva are lost or significantly impaired. These saliva-related alterations,
combined with poor oral hygiene and increased consumption of carbohydrate-rich foods, predispose
PWS patients to various oral diseases [2],[3].
One of the key components of saliva crucial for oral health are proteins like mucins, lysozyme,
peroxidases, lactoferrin, and defensins, which perform protective and antimicrobial functions. Several
studies have compared the total protein concentration in the saliva of PWS patients and healthy
individuals, revealing higher protein levels in PWS patients [4],[5]. Targeted analyses using methods
like blotting and ELISA have also compared the levels of specific proteins related to oral health, such
as MUC7 mucin and cystatins, as well as the glucose-homeostasis-related protein irisin, in unstimulated
saliva [4],[6]. However, comprehensive studies on the protein composition of saliva in PWS patients are
still lacking.
Objective: The aim of this proposal is to compare the proteome of stimulated saliva of PWS patients
and healthy individuals using a high-throughput method, specifically high-performance liquid
chromatography coupled with mass spectrometry (LC-MS/MS), employing a bottom-up approach. The
choice of stimulated saliva is due to its larger obtainable volume compared to unstimulated saliva, which
is particularly important for PWS patients who produce small volumes of viscous saliva.
imaging methods that will improve the early recognition and personalized treatment of atrial failure. The
proposed project will be embedded in existing research structure within the Medical University of Warsaw,
namely DIPE project (NCT06381245).
The aim of this research project is:
1) To characterize the specific patient’s profiles in HS disease by miRNAs assessment using in silico
prediction analysis, and thereafter validation.
2) To compare the impact of different treatment regimens (antibiotics vs TNFα inhibitors) on the change
in expression of miRNAs (selected by bioinformatic analysis) associated with pathological processes such as
inflammation, autophagy, oxidative stress and fibrosis in HS patients.
3) Analysis of the association between: (i) changes in the expression of specific miRNAs and (ii) markers of
inflammation, autophagy, oxidative stress, fibrosis processes and (iii) clinical manifestations of HS
(distribution, advancement, number and severity of skin lesions).
4) Evaluation of the usefulness of the obtained results in clinical practice, construction of a dedicated scale
combining evaluation of miRNAs expression, standard parameters of inflammation, autophagy, oxidative
stress, fibrosis and ultrasound features in order to monitor and evaluate clinical efficacy of treatment in a
selected drug regimen.