Please use this identifier to cite or link to this item: https://hdl.handle.net/11147/5870
Title: Neuraminidase-1 contributes significantly to the degradation of neuronal B-series gangliosides but not to the bypass of the catabolic block in Tay-Sachs mouse models
Authors: Timur, Zehra Kevser
Akyıldız Demir, Seçil
Marsching, C.
Sandhoff, R.
Seyrantepe, Volkan
Timur, Zehra Kevser
Akyıldız Demir, Seçil
Seyrantepe, Volkan
Izmir Institute of Technology. Molecular Biology and Genetics
Keywords: Tay-Sachs
Ganglioside
Hexosaminidase
Neuraminidase
Issue Date: Aug-2015
Publisher: Elsevier Ltd.
Source: Timur, Z.K., Akyıldız Demir, S., Marsching, C., Sandhoff, R., and Seyrantepe, V. (2015). Neuraminidase-1 contributes significantly to the degradation of neuronal B-series gangliosides but not to the bypass of the catabolic block in Tay-Sachs mouse models. Molecular Genetics and Metabolism Reports, 4, 72-82. doi:10.1016/j.ymgmr.2015.07.004
Abstract: TaySachs disease is a severe lysosomal storage disorder caused bymutations in the HEXA gene coding for? subunit of lysosomal β-Hexosaminidase A enzyme, which converts GM2 to GM3 ganglioside. HexA mice, depleted of the β-Hexosaminidase A iso-enzyme, remain asymptomatic up to 1 year of age because of a metabolic bypass by neuraminidase(s). These enzymes remove a sialic acid residue converting GM2 to GA2,which is further degraded by the still intact β-Hexosaminidase B iso-enzyme into lactosylceramide. A previously identified ganglioside metabolizing neuraminidase, Neu4, is abundantly expressed in the mouse brain and has activity against gangliosides like GM2 in vitro. Neu4 mice showed increased GD1a and decreased GM1 ganglioside in the brain suggesting the importance of the Neu4 in ganglioside catabolism. Mice with targeted disruption of both HexA and Neu4 genes showed accumulating GM2 ganglioside and epileptic seizures with 40% penetrance, indicating that the neuraminidase Neu4 is a modulatory gene, but may not be the only neuraminidase contributing to the metabolic bypass in HexA mice. Therefore, we elucidated the biological role of neuraminidase-1 in ganglioside degradation in mouse. Analysis of HexANeu1 and HexANeu4Neu1 mice models showed significant contribution of neuraminidase-1 on B-series ganglioside degradation in the brain. Therefore, we speculate that other neuraminidase/neuraminidases such as Neu2 and/or Neu3 might be also involved in the ganglioside degradation pathway in HexA mice.
URI: https://doi.org/10.1016/j.ymgmr.2015.07.004
http://hdl.handle.net/11147/5870
ISSN: 2214-4269
Appears in Collections:Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik
PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection

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