Autophagic flux is impaired in the brain tissue of Tay-Sachs disease mouse model

Tay-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-/- mo...

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Autores principales: Sengul, Tugce, Can, Melike, Ateş, Nurselin, Seyrantepe, Volkan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10019743/
https://www.ncbi.nlm.nih.gov/pubmed/36928510
http://dx.doi.org/10.1371/journal.pone.0280650
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author Sengul, Tugce
Can, Melike
Ateş, Nurselin
Seyrantepe, Volkan
author_facet Sengul, Tugce
Can, Melike
Ateş, Nurselin
Seyrantepe, Volkan
author_sort Sengul, Tugce
collection PubMed
description Tay-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.
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spelling pubmed-100197432023-03-17 Autophagic flux is impaired in the brain tissue of Tay-Sachs disease mouse model Sengul, Tugce Can, Melike Ateş, Nurselin Seyrantepe, Volkan PLoS One Research Article Tay-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. Public Library of Science 2023-03-16 /pmc/articles/PMC10019743/ /pubmed/36928510 http://dx.doi.org/10.1371/journal.pone.0280650 Text en © 2023 Sengul et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Sengul, Tugce
Can, Melike
Ateş, Nurselin
Seyrantepe, Volkan
Autophagic flux is impaired in the brain tissue of Tay-Sachs disease mouse model
title Autophagic flux is impaired in the brain tissue of Tay-Sachs disease mouse model
title_full Autophagic flux is impaired in the brain tissue of Tay-Sachs disease mouse model
title_fullStr Autophagic flux is impaired in the brain tissue of Tay-Sachs disease mouse model
title_full_unstemmed Autophagic flux is impaired in the brain tissue of Tay-Sachs disease mouse model
title_short Autophagic flux is impaired in the brain tissue of Tay-Sachs disease mouse model
title_sort autophagic flux is impaired in the brain tissue of tay-sachs disease mouse model
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10019743/
https://www.ncbi.nlm.nih.gov/pubmed/36928510
http://dx.doi.org/10.1371/journal.pone.0280650
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