Autophagic flux is impaired in the brain tissue of Tay-Sachs disease mouse model.
Tugce SengulMelike CanNurselin AteşVolkan SeyrantepePublished in: PloS one (2023)
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.
Keyphrases
- mouse model
- cell death
- end stage renal disease
- white matter
- resting state
- newly diagnosed
- ejection fraction
- oxidative stress
- multiple sclerosis
- functional connectivity
- prognostic factors
- type diabetes
- endoplasmic reticulum stress
- signaling pathway
- early onset
- genome wide
- single cell
- brain injury
- insulin resistance
- physical activity
- weight gain
- deep learning
- blood brain barrier
- drug induced
- replacement therapy
- protein kinase
- high speed
- genome wide identification
- high resolution mass spectrometry
- high fat diet induced