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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Published in:PloS one 2023-03, Vol.18 (3), p.e0280650-e0280650
Main Authors: Sengul, Tugce, Can, Melike, Ateş, Nurselin, Seyrantepe, Volkan
Format: Article
Language:English
Subjects:
Accumulation
Analysis
Animal tissues
Animals
Antibodies
Autophagy
Autophagy (Cytology)
Autophagy - physiology
beta-N-Acetylhexosaminidases - genetics
beta-N-Acetylhexosaminidases - metabolism
Biology and Life Sciences
Brain
Brain - metabolism
Brain - pathology
Care and treatment
Cell death
Central nervous system
Diagnosis
Disease
Disease Models, Animal
Fluctuations
G(M2) Ganglioside - therapeutic use
Ganglioside GM2
Gangliosides
Gene mutations
Genes
Genetic aspects
Health aspects
Hexosaminidase A - metabolism
Homeostasis
Medicine and Health Sciences
Membranes
Mice
Modelling
Mutation
Neurodegeneration
Neurological diseases
Pathology
Phagocytosis
Phagosomes
Phenotypes
Proteins
Research and Analysis Methods
Tay-Sachs disease
Tay-Sachs Disease - metabolism
Tay-Sachs Disease - pathology
Therapeutic targets
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Seyrantepe, Volkan
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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subjects Accumulation
Analysis
Animal tissues
Animals
Antibodies
Autophagy
Autophagy (Cytology)
Autophagy - physiology
beta-N-Acetylhexosaminidases - genetics
beta-N-Acetylhexosaminidases - metabolism
Biology and Life Sciences
Brain
Brain - metabolism
Brain - pathology
Care and treatment
Cell death
Central nervous system
Diagnosis
Disease
Disease Models, Animal
Fluctuations
G(M2) Ganglioside - therapeutic use
Ganglioside GM2
Gangliosides
Gene mutations
Genes
Genetic aspects
Health aspects
Hexosaminidase A - metabolism
Homeostasis
Medicine and Health Sciences
Membranes
Mice
Modelling
Mutation
Neurodegeneration
Neurological diseases
Pathology
Phagocytosis
Phagosomes
Phenotypes
Proteins
Research and Analysis Methods
Tay-Sachs disease
Tay-Sachs Disease - metabolism
Tay-Sachs Disease - pathology
Therapeutic targets
title Autophagic flux is impaired in the brain tissue of Tay-Sachs disease mouse model
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