Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7148
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Article Citation - WoS: 2Citation - Scopus: 2Combined Treatment of Ketogenic Diet and Propagermanium Reduces Neuroinflammation in Tay-Sachs Disease Mouse Model(Springer/Plenum Publishers, 2025) Inci, Orhan Kerim; Seyrantepe, VolkanTay-Sachs disease is a rare lysosomal storage disorder caused by beta-Hexosaminidase A enzyme deficiency causing abnormal GM2 ganglioside accumulation in the central nervous system. GM2 accumulation triggers chronic neuroinflammation due to neurodegeneration-based astrogliosis and macrophage activity with the increased expression level of Ccl2 in the cortex of a recently generated Tay-Sachs disease mouse model Hexa-/-Neu3-/-. Propagermanium blocks the neuroinflammatory response induced by Ccl2, which is highly expressed in astrocytes and microglia. The ketogenic diet has broad potential usage in neurological disorders, but the knowledge of the impact on Tay-Sach disease is limited. This study aimed to display the effect of combining the ketogenic diet and propagermanium treatment on chronic neuroinflammation in the Tay-Sachs disease mouse model. Hexa-/-Neu3-/- mice were placed into the following groups: (i) standard diet, (ii) ketogenic diet, (iii) standard diet with propagermanium, and (iv) ketogenic diet with propagermanium. RT-PCR and immunohistochemistry analyzed neuroinflammation markers. Behavioral analyses were also applied to assess phenotypic improvement. Notably, the expression levels of neuroinflammation-related genes were reduced in the cortex of 140-day-old Hexa-/-Neu3-/- mice compared to beta-Hexosaminidase A deficient mice (Hexa-/-) after combined treatment. Immunohistochemical analysis displayed correlated results with the RT-PCR. Our data suggest the potential to implement combined treatment to reduce chronic inflammation in Tay-Sachs and other lysosomal storage diseases.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.