Cited by 337Protease and Inhibitor MechanismsCalpain Protease Function and RegulationAutophagy in Disease and Therapy

Neuronal loss and brain atrophy in mice lacking cathepsins B and L

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Felbor, Ute, Kessler, Benedikt, Mothes, Walther, Goebel, Hans H., Ploegh, Hidde L., Bronson, Roderick T., Olsen, Bjorn R.·2002·Proceedings of the National Academy of Sciences

Abstract

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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Authors
Felbor, U., Kessler, B., Mothes, W., Goebel, H. H., Ploegh, H. L., Bronson, R. T., & Olsen, B. R.
Affiliations
Tufts University (US)
Venue
Proceedings of the National Academy of Sciences
Published
2002-06-04
Volume
99
Issue
12
Pages
7883-7888
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
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
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
  • Health Sciences › Medicine › Epidemiology › 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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