PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7645
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Article Citation - WoS: 1Citation - Scopus: 1Abnormally Accumulated Gm2 Ganglioside Contributes To Skeletal Deformity in Tay-Sachs Mice(Springer Heidelberg, 2024) Demir, Secil Akyildiz; Seyrantepe, Volkan; Seyrantepe, Volkan; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of TechnologyTay-Sachs Disease is a rare lysosomal storage disorder caused by mutations in the HEXA gene, responsible for the degradation of ganglioside GM2. In addition to progressive neurodegeneration, Tay-Sachs patients display bone anomalies, including kyphosis. Tay-Sachs disease mouse model (Hexa-/-Neu3-/-) shows both neuropathological and clinical abnormalities of the infantile-onset disease phenotype. In this study, we investigated the effects of GM2 accumulation on bone remodeling activity. Here, we evaluated the bone phenotype of 5-month-old Hexa-/-Neu3-/- mice with age-matched control groups using gene expression analysis, bone plasma biomarker analysis, and micro-computed tomography. We demonstrated lower plasma alkaline phosphatase activity and calcium levels with increased tartrate-resistant acid phosphatase levels, indicating reduced bone remodeling activity in mice. Consistently, gene expression analysis confirmed osteoblast reduction and osteoclast induction in the femur of mice. Micro-computed tomography and analysis show reduced trabecular bone volume, mineral density, number, and thickness in Hexa-/-Neu3-/- mice. In conclusion, we demonstrated that abnormal GM2 ganglioside accumulation significantly triggers skeletal abnormality in Tay-Sachs mice. We suggest that further investigation of the molecular basis of bone structure anomalies is necessary to elucidate new therapeutic targets that prevent the progression of bone symptoms and improve the life standards of Tay-Sachs patients.Review Citation - WoS: 7Gangliosides as Therapeutic Targets for Neurodegenerative Diseases(Hindawi Ltd, 2024) Inci, Orhan Kerim; Seyrantepe, Volkan; Basirli, Hande; Can, Melike; Yanbul, Selman; Seyrantepe, Volkan; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of TechnologyGangliosides, sialic acid-containing glycosphingolipids, are abundant in cell membranes and primarily involved in controlling cell signaling and cell communication. The altered ganglioside pattern has been demonstrated in several neurodegenerative diseases, characterized during early-onset or infancy, emphasizing the significance of gangliosides in the brain. Enzymes required for the biosynthesis of gangliosides are linked to several devastating neurological disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), hereditary spastic paraplegia (HSP). In this review, we summarized not only the critical roles of biosynthetic enzymes and their inhibitors in ganglioside metabolism but also the efficacy of treatment strategies of ganglioside to address their significance in those diseases.