| First Author | Takamura A | Year | 2008 |
| Journal | Biochem Biophys Res Commun | Volume | 367 |
| Issue | 3 | Pages | 616-22 |
| PubMed ID | 18190792 | Mgi Jnum | J:131346 |
| Mgi Id | MGI:3773518 | Doi | 10.1016/j.bbrc.2007.12.187 |
| Citation | Takamura A, et al. (2008) Enhanced autophagy and mitochondrial aberrations in murine G(M1)-gangliosidosis. Biochem Biophys Res Commun 367(3):616-22 |
| abstractText | G(M1)-gangliosidosis is an autosomal recessive lysosomal lipid storage disorder, caused by mutations of the lysosomal beta-galactosidase (beta-gal) and results in the accumulation of G(M1). The underlying mechanisms of neurodegeneration are poorly understood. Here we demonstrate increased autophagy in beta-gal-deficient (beta-gal(-/-)) mouse brains as evidenced by elevation of LC3-II and beclin-1 levels. Activation of autophagy in the beta-gal(-/-) brain was found to be accompanied with enhanced Akt-mTOR and Erk signaling. In addition, the mitochondrial cytochrome c oxidase activity was significantly decreased in brains and cultured astrocytes from beta-gal(-/-) mouse. Mitochondria isolated from beta-gal(-/-) astrocytes were morphologically abnormal and had a decreased membrane potential. These cells were more sensitive to oxidative stress than wild type cells and this sensitivity was suppressed by ATP, an autophagy inhibitor 3-methyladenine and a pan-caspase inhibitor z-VAD-fmk. These results suggest activation of autophagy leading to mitochondrial dysfunction in the brain of G(M1)-gangliosidosis. |
