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" Nörominidaz 1 ve gm3 sentaz enzimlerinin glikolipit metabolizmasındaki birleşik biyolojik rolünün araştırılması "
Can, Melike
Seyrantepe, Volkan
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Latin Dissertation
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| Language of Document
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English
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| Record Number
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1112218
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| Doc. No
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TLpq2522823070
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| Main Entry
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Can, Melike
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Seyrantepe, Volkan
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| Title & Author
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Nörominidaz 1 ve gm3 sentaz enzimlerinin glikolipit metabolizmasındaki birleşik biyolojik rolünün araştırılması\ Can, MelikeSeyrantepe, Volkan
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| College
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Izmir Institute of Technology (Turkey)
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| Date
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2020
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2020
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| Degree
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Master's
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| Page No
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158
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| Abstract
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Gangliosides are sialic acid-containing glycosphingolipids, and commonly expressed in nervous system. GM3 Synthase is responsible for production of GM3 ganglioside known as precursor of a- and b- series gangliosides. Sialidases catalyze removing of sialic acid residues from sialoglycoconjugates and classified based on subcellular localization. Lysosomal Neu1 sialidase is responsible for catabolism of glycolipids, glycoproteins and oligosaccharides. Mutations of lysosomal Neu1 sialidase cause sialidosis and Neu1-/- mice mimic symptoms seen in patients. Glycosphingolipid accumulation in visceral organs of sialidosis patients was notified previously, and it was also reported the GM3 ganglioside as substrate of lysosomal sialidase in vitro. However, effect of Neu1 sialidase in the case of complex ganglioside deficiency in brain remains unclear. In the concept of research, we aimed to understand biological role of lysosomal Neu1 sialidase alone and combined with GM3S in ganglioside metabolism in vivo. In accordance with this purpose, cortex, cerebellum and thalamus tissues of 2- and 5-month old Neu1-/-GM3S-/-, Neu1-/- and GM3S-/- mice were compared with age-matched control group using molecular biological, histological, immunohistochemistry and behavioral analyses. Alterations in ganglioside metabolism, oligosaccharide pattern and cellular processes (ER-oxidative stress, apoptosis), structural abnormalities, glycoconjugate accumulation, loss of neurons and oligodendrocytes in addition to age dependent behavioral impairments in motor function, memory and muscle strength were demonstrated in single and double knock-out mice. In regard of these results, we have concluded that altered glycosphingolipid metabolism with accumulated secondary metabolites like oligosaccharides affect cellular processes and brain pathology resulting in behavioral abnormalities in age dependent and region specific manner.
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Genetics
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Molecular biology
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