Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7148
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Article Mass Spectrometric Profiling Reveals Alterations in N-Glycans and O-Glycans in Tay-Sachs Disease Under Autophagy-Induced Conditions(Springer, 2025) Can, Melike; Basirli, Hande; Jin, Chunsheng; Karlsson, Niclas G.; Bojar, Daniel; Seyrantepe, VolkanTay-Sachs disease is a rare neurodegenerative disorder caused by mutations in the HEXA gene. The HEXA gene encodes the alpha-subunit of the enzyme beta-hexosaminidase A, which degrades GM2 ganglioside. Previously, we identified impaired autophagy in the brains of a mouse model of Tay-Sachs disease, which exhibited neuropathological and clinical abnormalities. Moreover, we demonstrated autophagosome clearance in Tay-Sachs cells under lithium-induced conditions. Here, we further aimed to evaluate N- and O-glycan changes in these cells and examine whether glycan alterations are linked to ER stress. The profiles of N- and O-glycans were analyzed using LC-MS/MS in fibroblasts and neuroglial cells from 5-month-old Hexa-/-Neu3-/- mice and neuroglial cells from Tay-Sachs patients under lithium induction and nutrient deprivation. The expression levels of ER stress-related markers were assessed using qRT-PCR and Western blot analyses. We demonstrated higher levels of high mannose and lower levels of complex types of N-glycans, along with increased O-glycan levels in Tay-Sachs cells. Compared to control groups, we observed upregulated expression of endoplasmic reticulum (ER) stress-related markers, CHOP and ATF-6, in Tay-Sachs cells. Our study demonstrated that autophagy induction causes the degradation of accumulated high-mannose N-glycans and O-glycans, which is associated with the downregulation of ER stress-related genes in Tay-Sachs cells. Our study is the first to show this phenomenon in Tay-Sachs cells and suggests the presence of ER stress-mediated autophagy. Therefore, targeting glycans through autophagy induction could offer therapeutic benefits to patients with Tay-Sachs disease in future studies.Article Citation - WoS: 1Citation - Scopus: 1Imbalance in Redox Homeostasis Is Associated With Neurodegeneration in the Murine Model of Tay-Sachs Disease(Springer, 2025) Basirli, Hande; Ates, Nurselin; Seyrantepe, VolkanBackgroundTay-Sachs disease is a neurodegenerative disorder characterized by a build-up of GM2 ganglioside in the brain, which results in progressive central nervous system dysfunction. Our group recently generated Hexa-/-Neu3-/- mice, a murine model with neuropathological abnormalities similar to the infantile form of Tay-Sachs disease. Previously, we reported progressive neurodegeneration with neuronal loss in the brain sections of Hexa-/-Neu3-/- mice. However, the relationship between the severity of neurodegeneration and the imbalance in redox homeostasis was not yet clarified in Hexa-/-Neu3-/- mice. Here, we evaluated whether neurodegeneration is associated with oxidative stress in the tissues and cells of Hexa-/-Neu3-/- mice and neuroglia cells from Tay-Sachs patients.Methods and resultsCell death and oxidative stress-related markers were evaluated in four brain regions and fibroblasts of 5-month-old WT, Hexa-/-, Neu3-/-, and Hexa-/-Neu3-/- mice and human neuroglia cells using Western blot, RT-PCR, and immunohistochemistry analyses. We further analyzed oxidative stress levels in the samples using flow cytometry analyses. We discovered neuronal death, alterations in intracellular ROS levels, and damaging effects of oxidative stress, especially in the cerebellum and fibroblasts of Hexa-/-Neu3-/- mice.ConclusionsOur results showed that alteration in redox homeostasis might be related to neurodegeneration in the murine model of Tay-Sachs Disease. These findings suggest that targeting the altered redox balance and increased oxidative stress might be a rational therapeutic approach for alleviating neurodegeneration and treating Tay-Sachs disease.