The DOI matches its Crossref record; 43 of the 44 references it cites were found in a registry or an index.
Neuronal loss and brain atrophy in mice lacking cathepsins B and L
Open accessAbstract
Cathepsins B and L are widely expressed cysteine proteases implicated in both intracellular proteolysis and extracellular matrix remodeling. However, specific roles remain to be validated in vivo . Here we show that combined deficiency of cathepsins B and L in mice is lethal during the second to fourth week of life. Cathepsin B −/− /L −/− mice reveal a degree of brain atrophy not previously seen in mice. This is because of massive apoptosis of select neurons in the cerebral cortex and the cerebellar Purkinje and granule cell layers. Neurodegeneration is accompanied by pronounced reactive astrocytosis and is preceded by an accumulation of ultrastructurally and biochemically unique lysosomal bodies in large cortical neurons and by axonal enlargements. Our data demonstrate a pivotal role for cathepsins B and L in maintenance of the central nervous system.
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“CTSD protein levels are elevated in CTSB/CTSL double KO mice (Felbor et al., 2002), suggesting intralysosomal CTSD proteolysis, even though the involved protease(s) are unclear.”
From Lysosomal Dysfunction in Down Syndrome Is APP-Dependent and Mediated by APP-βCTF (C99) (2019) · cites this paper as Felbor et al., 2002
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Chang, D., Nalls, M. A., Hallgrímsdóttir, I. B., Hunkapiller, J., van der Brug, M., Cai, F., International Parkinson's Disease Genomics Consortium, 23andMe Research Team, Kerchner, G. A., Ayalon, G., et al. (2017) · Nature Genetics · doi:10.1038/ng.3955 · Cited by 1,112
Metadata
- Authors
- Felbor, U., Kessler, B., Mothes, W., Goebel, H. H., Ploegh, H. L., Bronson, R. T., & Olsen, B. R.
- Affiliations
- Tufts University (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2002-06-04
- Volume
- 99
- Issue
- 12
- Pages
- 7883-7888
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC122989
- OpenAlex
- W1984073321
- Cited by
- 334
- References
- 44
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 9 · 2023: 10 · 2022: 17 · 2021: 7 · 2020: 16 · 2019: 12 · 2018: 8 · 2017: 9 · 2016: 15 · 2015: 14 · 2014: 11 · 2013: 19 · 2012: 16
- FWCI
- 5.31
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
- Funders
- AstraZeneca
- Deutsche Forschungsgemeinschaft
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Calpain Protease Function and Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Keywords
- cathepsin B, cathepsin L, cysteine protease, neuronal loss, brain atrophy, neurodegeneration, apoptosis, reactive astrogliosis, Purkinje cells, granule cells, cerebral cortex, cerebellum, embryonic lethality, knockout mice
- MeSH terms
- Animals, Atrophy, Brain, Cathepsin B, Cathepsins, Cerebellum, Cysteine Endopeptidases, Genotype, Lysosomes, Neurons, Endosomes, Apoptosis, Mice, Knockout, Mice, Cathepsin L
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