| First Author | Cheng S | Year | 2017 |
| Journal | J Neurochem | Volume | 142 |
| Issue | 2 | Pages | 297-304 |
| PubMed ID | 28429406 | Mgi Jnum | J:243211 |
| Mgi Id | MGI:5907925 | Doi | 10.1111/jnc.14048 |
| Citation | Cheng S, et al. (2017) Haplodeficiency of Cathepsin D does not affect cerebral amyloidosis and autophagy in APP/PS1 transgenic mice. J Neurochem 142(2):297-304 |
| abstractText | Autophagy and lysosomal function are important for protein homeostasis and their dysfunction have been associated with Alzheimer's disease (AD). Increased immunoreactivities of an important lysosomal protease, cathepsin D (Cat D), are evident in amyloid plaques and neurons in patients with AD. This study tests the hypothesis that deleting one allele of the cathepsin D gene (Ctsd) impacts cerebral beta-amyloidosis in amyloid-beta precursor protein (APP)sw/PS1dE9 (APP/PS1) double transgenic mice. Despite a significant 38% decrease in Cat D level in APP/PS1/Ctsd+/- compared with APP/PS1/Ctsd+/+ mice, no changes in steady state levels and deposition of Abeta were found in the brain. There were also no differences in APP processing, the levels of two other Abeta-degrading proteases, the levels of autophagy related protein, such as LAMP2, P62, LC3-I, LC3-II, and Beclin-1, or the markers of neuroinflammation, observed between the APP/PS1/Ctsd+/+ and APP/PS1/Ctsd+/- mice. Our findings demonstrate that in wild-type mice, Cat D protein levels are either in excess or redundant with other factors in the brain, and at least one allele of Ctsd is dispensable for cerebral beta-amyloidosis and autophagy in APP/PS1 transgenic mice. |
