| First Author | Sengul T | Year | 2023 |
| Journal | PLoS One | Volume | 18 |
| Issue | 3 | Pages | e0280650 |
| PubMed ID | 36928510 | Mgi Jnum | J:339199 |
| Mgi Id | MGI:7445939 | Doi | 10.1371/journal.pone.0280650 |
| Citation | Sengul T, et al. (2023) Autophagic flux is impaired in the brain tissue of Tay-Sachs disease mouse model. PLoS One 18(3):e0280650 |
| abstractText | Tay-Sachs disease is a lethal lysosomal storage disorder caused by mutations in the HexA gene encoding the alpha subunit of the lysosomal beta-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. |
