Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik
Permanent URI for this collectionhttps://hdl.handle.net/11147/9
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Article Citation - WoS: 4Citation - Scopus: 4Autophagic Flux Is Impaired in the Brain Tissue of Tay-Sachs Disease Mouse Model(Public Library of Science, 2023) Şengül, Tuğçe; Can, Melike; Ateş, Nurselin; Seyrantepe, VolkanTay-Sachs disease is a lethal lysosomal storage disorder caused by mutations in the HexA gene encoding the α subunit of the lysosomal β-hexosaminidase enzyme (HEXA). Abnormal GM2 ganglioside accumulation causes progressive deterioration in the central nervous system in Tay-Sachs patients. Hexa-/-mouse model failed to display abnormal phenotype. Recently, our group generated Hexa-/-Neu3-/-mouse showed severe neuropathological indications similar to Tay-Sachs patients. Despite excessive GM2 ganglioside accumulation in the brain and visceral organs, the regulation of autophagy has not been clarified yet in the Tay-Sachs disease mouse model. Therefore, we investigated distinct steps of autophagic flux using markers including LC3 and p62 in four different brain regions from the Hexa-/-Neu3-/-mice model of Tay-Sachs disease. Our data revealed accumulated autophagosomes and autophagolysosomes indicating impairment in autophagic flux in the brain. We suggest that autophagy might be a new therapeutic target for the treatment of devastating Tay-Sachs disease. © 2023 Sengul et al.Article Citation - WoS: 6Citation - Scopus: 6Analysis of Brain Lipids in the Early-Onset Tay–sachs Disease Mouse Model With the Combined Deficiency of Β-Hexosaminidase a and Neuraminidase 3(Frontiers Media S.A., 2022) Can, Melike; Şengül, Tuğçe; Akyıldız Demir, Seçil; İnci, Orhan K.; Basırlı, Hatice Hande; Seyrantepe, VolkanTay–Sachs disease is an autosomal recessively inherited lysosomal storage disease that results from loss-of-function mutations in the HEXA gene coding βhexosaminidase A. HEXA gene deficiency affects the central nervous system owing to GM2 ganglioside accumulation in lysosomes resulting in progressive neurodegeneration in patients. We recently generated a novel mice model with a combined deficiency of βhexosaminidase A and neuraminidase 3 (Hexa−/−Neu3−/−) that mimics both the neuropathological and clinical abnormalities of early-onset Tay–Sachs disease. Here, we aimed to explore the secondary accumulation of lipids in the brain of Hexa−/ −Neu3−/− mice.Conference Object Abnormal Gm2 Accumulation Alters the Function of the Autophagic Pathway in Early-Onset Tay-Sachs Disease Mouse Model(Academic Press, 2018) Seyrantepe, Volkan; Ateş, Nurselin; Can, Melike; Şengül, Tuğçe; Akyıldız Demir, SeçilTay-Sachs disease (TSD) is an inborn error of metabolism, a prototypical lysosomal disease of the nervous system. In humans, the fatal infantile acute form is the most common, and with no current treatment, prevention and palliative care the only options. TSD mice did not mimic human infantile TSD, and although mice showed some early pathology and storage of GM2 ganglioside, clinical disease would take many months to develop. The extremely mild disease in the TSD mice was likely due to a biochemical bypass, a neuraminidase. We recently demostrated that at least one of the principal murine neuraminidase, Neu3, responsible for the biochemical bypass in the catabolism of the GM2 ganglioside.