Abstract |
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 β- amyloidosis in amyloid-β 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 Aβ were found in the brain. There were also no differences in APP processing, the levels of two other Aβ-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 β- amyloidosis and autophagy in APP/PS1 transgenic mice.
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Authors | Shaowu Cheng, Willayat Y Wani, David A Hottman, Angela Jeong, Dongfeng Cao, Kyle J LeBlanc, Paul Saftig, Jianhua Zhang, Ling Li |
Journal | Journal of neurochemistry
(J Neurochem)
Vol. 142
Issue 2
Pg. 297-304
(07 2017)
ISSN: 1471-4159 [Electronic] England |
PMID | 28429406
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | © 2017 International Society for Neurochemistry. |
Chemical References |
- Amyloid beta-Peptides
- Amyloid beta-Protein Precursor
- Oligopeptides
- PS1 antigen
- Cathepsin D
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Topics |
- Alzheimer Disease
(genetics, metabolism)
- Amyloid beta-Peptides
(metabolism)
- Amyloid beta-Protein Precursor
(genetics, metabolism)
- Animals
- Autophagy
(genetics, physiology)
- Brain
(metabolism)
- Cathepsin D
(genetics, metabolism)
- Disease Models, Animal
- Mice, Transgenic
- Neurons
(metabolism)
- Oligopeptides
(genetics, metabolism)
- Plaque, Amyloid
(metabolism)
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