Master Degree / Yüksek Lisans Tezleri

Permanent URI for this collectionhttps://hdl.handle.net/11147/3008

Browse

Filters

20242

Settings

Has files: YesSubject: search.filters.subject.Molecular Medicine

Search Results

Now showing 1 - 2 of 2
  • Master Thesis
    Identification of Neuroinflammatory Markers in a Mouse Model With a Deficiency of Neu1
    (01. Izmir Institute of Technology, 2024) Seyrantepe, Volkan; Ada, Ebru; Seyrantepe, Volkan
    Lysosomal neuraminidase 1 is responsible for sialic acid removal from oligosaccharides and glycoconjugates. Neu1 sialidase forms enzyme complex with protective protein cathepsin A, and glycosidase β-galactosidase. Mutations in Neu1 sialidase cause sialidosis, and Neu1-/- mice show symptoms of sialidosis patients. GM3 ganglioside is defined as substrate of lysosomal sialidase in vitro, and marked increase in GM3, GD3, and GM4 ganglioside levels in brain, spleen and liver autopsy tissues of sialidosis patients. Additionally, it was monitored that Neu1 has regulatory roles in immune response; expression of interleukins, activation of Toll-like receptor, and production of NF-kB in immune cells. However, relationship between inflammatory pathways and secondary lipid metabolisms in Neu1 sialidase deficiency remains unclear. Here, we aimed to investigate secondary lipid alterations and inflammatory response in tissues of Neu1-/- mice. In this study, lipidomic, molecular, histological and immunohistochemical analyses were performed in brain, spleen and kidney tissues of 2- and 5-month-old Neu1-/- mice. Decreasing levels of secondary lipids (phosphotidylcholine, phosphatidylethanolamine, and phosphotidylinositol) and elevated levels of pro-inflammatory cytokines, glycoconjugate accumulations, morphological degenerations, oligodendrocyte and neuronal loss, astrogliosis, and microgliosis were observed in brain, spleen and kidney of 2- and 5-month-old Neu1-/- mice. In the light of our findings, reduced levels of glycerophospholipids may be considered as biomarkers of activated inflammatory response in Type II sialidosis mice model. In the future studies, novel therapeutic strategies can target these altered glycerophospholipids, and their regulation can be crucial for alleviation of pathogenesis in sialidosis patients.
  • Master Thesis
    Investigation of Biomarkers Using Lipidome-Based Research Analysis in Sialidosis
    (01. Izmir Institute of Technology, 2024) Gümüş, İlker; Seyrantepe, Volkan
    Neuraminidase 1, also known as N-acetyl-α-neuraminidase, is an enzyme found in lysosomes and encoded by the NEU1 gene. This enzyme is responsible for eliminating terminal sialic acids from glycoproteins and oligosaccharides. When mutations occur in the NEU1 gene, it leads to a particular lysosomal storage disorder known as sialidosis. Sialidosis is a rare genetic disorder that is inherited in an autosomal recessive manner. Sialidosis is classified into two subtypes: Type I, which has a later onset and Type II, which presents with early onset. In previous studies, an increase in glycolipid levels in visceral organs, and accumulation of sialyloligosaccharides and sialoglycoproteins were reported. However, the effect of NEU1 sialidase on secondary lipid expression levels in sialidosis pathology remains unknown. The relationship between lipid expression levels and inflammation of human and mice sialidosis fibroblasts cell lines was analyzed for the first time in this study. To understand the connection between secondary lipid alterations and inflammation in sialidosis molecular biological approaches and shotgun lipidome analysis were followed. The link between the secondary lipid alterations and its association with sialidosis was determined in our research. We have concluded that the findings not only provide the elucidation of the lipidome characteristics in sialidosis models of mice and patients, but they also have the potential to establish a connection between the lipidome features and the occurrence of neuroinflammation in sialidosis. Grasping the correlation between the changes in secondary lipids and inflammation may offer therapeutic strategies for sialidosis patients by modulating the expression of secondary lipids.