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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“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
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation.
Gavrieli, Y., Sherman, Y., & Ben-Sasson, S. A. (1992) · The Journal of cell biology · doi:10.1083/jcb.119.3.493 · Cited by 9,444
Synaptic assembly of the brain in the absence of neurotransmitter secretion.
Verhage, M., Maia, A., Plomp, J., Brussaard, A., Heeroma, J., Vermeer, H., Toonen, R., Hammer, R., van den Berg, T. K., Missler, M., et al. (2000) · Science · doi:10.1126/science.287.5454.864 · Cited by 1,387
The Handbook of proteolytic enzymes
Barrett, A. J., Rawlings, N. D., & Woessner, J. F. (1998) · Cited by 1,119
Pycnodysostosis, a Lysosomal Disease Caused by Cathepsin K Deficiency
Gelb, B. D., Shi, G., Chapman, H. A., & Desnick, R. J. (1996) · Science · doi:10.1126/science.273.5279.1236 · Cited by 1,022
Impaired osteoclastic bone resorption leads to osteopetrosis in cathepsin-K-deficient mice
Säftig, P., Hunziker, E. B., Wehmeyer, O., Jones, S. J., BOYDE, A., Rommerskirch, W., Moritz, J. D., Schu, P. V., & FIGURA, K. V. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.23.13453 · Cited by 909
Vesa, J., Hellsten, E., Verkruyse, L. A., Camp, L. A., Rapola, J., Santavuori, P., Hofmann, S. L., & Peltonen, L. (1995) · Nature · doi:10.1038/376584a0 · Cited by 736
Guicciardi, M. E., Deussing, J. M., Miyoshi, H., Bronk, S. F., Svingen, P. A., Peters, C., Kaufmann, S. H., & Gores, G. J. (2000) · Journal of Clinical Investigation · doi:10.1172/jci9914 · Cited by 710
Cathepsin L: Critical Role in Ii Degradation and CD4 T Cell Selection in the Thymus
Nakagawa, T. Y., Roth, W., Wong, P., Nelson, A., Farr, A. G., Deussing, J. M., Villadangos, J. A., Ploegh, H. L., Peters, C., & Rudensky, A. Y. (1998) · Science · doi:10.1126/science.280.5362.450 · Cited by 675
Self-citationFoghsgaard, L., Wissing, D., Mauch, D., Lademann, U. A., Bastholm, L., Boes, M. L., Elling, F., Leist, M., & Jäättelä, M. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.153.5.999 · Cited by 629
Sleat, D. E., DONNELLY, R. J., Lackland, H., Liu, C., Sohár, I., Pullarkat, R. K., & Lobel, P. (1997) · Science · doi:10.1126/science.277.5333.1802 · Cited by 581
Flagged first, then by citations
1 of the 44 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- H Kirschke Handbook of Proteolytic Enzymes, eds A J Barrett, N D Rawlings, J F Woessner (Academic, San Diego), pp. 617–621 (1998).
Cited by
Sorted by citations
Items 301–337 of 337
Farizatto, K. L. G. (2014) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.5.2014.tde-09122014-133659
Lysosomes and Nonapoptotic Pathways
Kirkegaard‐Sørensen, T., Fehrenbacher, N., Gyrd‐Hansen, M., & Jüüttelü, M. (2006) · Wiley eBooks · doi:10.1002/9783527619665.ch23
Role of Lysosomal Enzymes in Parkinson’s Disease: Lesson from Gaucher’s Disease
Beccari, T., Balducci, C., Paciotti, S., Persichetti, E., Chiasserini, D., Castrioto, A., Tambasco, N., Rossi, A., Calabresi, P., Pagliardini, V., et al. (2011) · InTech eBooks · doi:10.5772/23552
Molecular biology of progressive myoclonus epilepsy of Unverricht-Lundborg type (EPM1)
Alakurtti, K. (2006) · Työväentutkimus Vuosikirja
Organelle specific mechanisms of neuronal cell death
Putkonen, N. (2012) · Työväentutkimus Vuosikirja
Cathepsin D Deficiency : Molecular and Cellular Mechanisms of Neurodegeneration
Partanen, S. (2006) · Työväentutkimus Vuosikirja
Regulación de la linfopoyesis B por la cisteín proteasa catepsina-L
Badano, M. N. (2012) · Repositorio Digital Institucional de la Universidad de Buenos Aires (Universidad de Buenos Aires)
The Paradoxical Roles of Cell Death Pathways in Immune Cells
McComb, S. (2013) · uO Research (University of Ottawa) · doi:10.20381/ruor-3097
β Synthesis and NLRP3-Mediated IL-1 β IL-1 - Multiple Cathepsins Promote Pro
Bogyo, M. S., Robertson, S. A., Orłowski, M., Colbert, J. D., & Sharma, S. (2015)
CELLULAR MECHANISMS OF NEURODEGENERATION
Partanen, S. (2006)
Odagiri, S., Mori, F., Tanji, K., Kuroda, N., & Wakabayashi, K. (2013) · Institutional Repositories DataBase (IRDB)
Organelle dysfunction modulates cholesterol biosynthesis pathway
Pereyra, L. (2019) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-7666
Cárcel‐Trullols, J. (2019) · International Clinical Neuroscience Journal · doi:10.15171/icnj.2020.02
Role of lysosomes in oxidative stress induced regulated cell death
Nagakannan, P. (2020) · Mspace (University of Manitoba)
Cavallo‐Medved, D., Sloane, B. F., & Moin, K. (2017) · Springer eBooks · doi:10.1007/978-3-319-67199-4_101523
Watts, C. K. W., & West, M. A. (2008) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.1139014.596119
Yu, D. M. T., Dauth, S., Margineanu, M. B., Snetkova, V., Rehders, M., Jordans, S., & Brix, K. (2022) · Applied Sciences · doi:10.3390/app12052608
A patient with pycnodysostosis presenting with seizures and porencephalic cysts
Kumar, S. (2014) · Journal of Neurosciences in Rural Practice · doi:10.1055/s-0039-1700334
Kirschke, H. (2007) · xPharm: The Comprehensive Pharmacology Reference · doi:10.1016/b978-008055232-3.62936-8
Kirschke, H. (2007) · xPharm: The Comprehensive Pharmacology Reference · doi:10.1016/b978-008055232-3.62915-0
Wicks, I. P., Kim, M. L., Souza, D. P. D., Narayana, V. K., Nguyen, N. C., & Sleebs, B. E. (2022) · Research Square · doi:10.21203/rs.3.rs-2299218/v1
The KT Jeang retrovirology prize 2024: Walther Mothes
Mothes, W. (2024) · Retrovirology · doi:10.1186/s12977-024-00649-8
Self-citationAdditional file 1 of Differential regulation of progranulin derived granulin peptides
Zhang, T., Du, H., Santos, M. N., Wu, X., Pagan, M. D., Trigiani, L. J., Nishimura, N., Reinheckel, T., & Hu, F. (2022) · Figshare · doi:10.6084/m9.figshare.19126284
The promising role of cathepsins as biomarkers and therapeutic targets in glioblastoma
Calcaterra, E., Labellarte, D., Hasan, A., Mannino, D., Scuderi, S. A., Luca, F. D., Ciappina, G., Marafioti, M., Caruso, G., Esposito, E., et al. (2026) · Discover Oncology · doi:10.1007/s12672-026-05192-w
Autophagy-lysosomal pathway in neurodegeneration
McDonough, S. R., Rao, A. K., McAleer, J. M., Babrowicz, B. M., & Sharma, M. (2026) · Molecular Neurodegeneration Advances · doi:10.1186/s44477-026-00041-0
Wu, Y.-J., Huang, Q., Ding, Z.-X., Fu, L., Yang, M., Peng, B., Hu, P.-B., & Liu, Y.-H. (2026) · Clinical and Translational Discovery · doi:10.1002/ctd2.70215
BindingDB Entry 3371: Dipeptidyl nitrile inhibitors of Cathepsin L.
BindingDB (2009) · UC San Diego · doi:10.7270/q2tt4pbm
BindingDB Entry 50041744: Design of selective Cathepsin inhibitors.
BindingDB (2013) · UC San Diego · doi:10.7270/q2n017s3
BindingDB Entry 50028291: 5-Aminopyrimidin-2-ylnitriles as cathepsin K inhibitors.
BindingDB (2010) · UC San Diego · doi:10.7270/q2571bwr
BindingDB Entry 50030742: Structure-guided development of selective TbcatB inhibitors.
BindingDB (2010) · UC San Diego · doi:10.7270/q2k074bp
MOLECULAR MECHANISMS BY WHICH c- ABL AND ARG MEDIATE MELANOMA INVASION AND METASTASIS
Ganguly, S. S. (2013) · UKnowledge (University of Kentucky)
Gopinathan, A. (2010) · ScholarlyCommons (University of Pennsylvania)
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
