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Haplodeficiency of Cathepsin D does not affect cerebral amyloidosis and autophagy in APP / PS 1 transgenic mice
Author(s) -
Cheng Shaowu,
Wani Willayat Y.,
Hottman David A.,
Jeong Angela,
Cao Dongfeng,
LeBlanc Kyle J.,
Saftig Paul,
Zhang Jianhua,
Li Ling
Publication year - 2017
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.14048
Subject(s) - cathepsin d , genetically modified mouse , amyloid precursor protein , autophagy , transgene , amyloidosis , biology , cathepsin , microbiology and biotechnology , chemistry , alzheimer's disease , medicine , biochemistry , gene , enzyme , disease , apoptosis
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/ PS 1dE9 ( APP / PS 1) double transgenic mice. Despite a significant 38% decrease in Cat D level in APP / PS 1/ Ctsd +/− compared with APP / PS 1/ 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 LAMP 2, P62, LC 3‐I, LC 3‐ II , and Beclin‐1, or the markers of neuroinflammation, observed between the APP / PS 1/ Ctsd +/+ and APP / PS 1/ 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 / PS 1 transgenic mice.

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