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

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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

DOI 10.1073/pnas.112632299PMC PMC122989

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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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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 924
Mutations in the palmitoyl protein thioesterase gene causing infantile neuronal ceroid lipofuscinosis
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
Cathepsin B contributes to TNF-α–mediated hepatocyte apoptosis by promoting mitochondrial release of cytochrome c
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-citation
Cathepsin B Acts as a Dominant Execution Protease in Tumor Cell Apoptosis Induced by Tumor Necrosis Factor
Foghsgaard, 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
Association of Mutations in a Lysosomal Protein with Classical Late-Infantile Neuronal Ceroid Lipofuscinosis
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
Role of cathepsin B in intracellular trypsinogen activation and the onset of acute pancreatitis
Halangk, W., Lerch, M. M., Brandt-Nedelev, B., Roth, W., Ruthenbürger, M., Reinheckel, T., Domschke, W., Lippert, H., Peters, C., & Deussing, J. M. (2000) · Journal of Clinical Investigation · doi:10.1172/jci9411 · Cited by 564
Loss-of-function mutations in the cathepsin C gene result in periodontal disease and palmoplantar keratosis
Toomes, C., James, J. A., Wood, A. J., Wu, C. L., McCormick, D., Lench, N., Hewitt, C., Moynihan, L. M., Roberts, E., Woods, C. G., et al. (1999) · Nature Genetics · doi:10.1038/70525 · Cited by 489
Secreted cathepsin L generates endostatin from collagen XVIII
Felbor, U., Dreier, L., Bryant, R. A. R., Ploegh, H. L., Olsen, B. R., & Mothes, W. (2000) · The EMBO Journal · doi:10.1093/emboj/19.6.1187 · Cited by 470
Self-citation
Mice deficient for the lysosomal proteinase cathepsin D exhibit progressive atrophy of the intestinal mucosa and profound destruction of lymphoid cells.
Säftig, P., Hetman, M., Schmahl, W. W., Weber, K., Heine, L., Mossmann, H., Köster, A., Heß, B., Evers, M., & FIGURA, K. V. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb00029.x · Cited by 439
Cathepsin D Deficiency Induces Lysosomal Storage with Ceroid Lipofuscin in Mouse CNS Neurons
Koike, M., Nakanishi, H., Säftig, P., Ezaki, J., Isahara, K., Ohsawa, Y., Schulz‐Schaeffer, W., Watanabe, T., Waguri, S., Kametaka, S., et al. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-18-06898.2000 · Cited by 391
Role for intracellular proteases in the processing and transport of class II HLA antigens.
Blum, J. S., & Cresswell, P. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.11.3975 · Cited by 337
Cathepsin L deficiency as molecular defect of furless: hyperproliferation of keratinocytes and pertubation of hair follicle cycling
Roth, W., Deussing, J. M., Botchkarev, V. A., Pauly-Evers, M., Säftig, P., Hafner, A., Schmidt, P. M., Schmahl, W. W., Scherer, J., Anton‐Lamprecht, I., et al. (2000) · The FASEB Journal · doi:10.1096/fj.99-0970com · Cited by 308
Inhibitors of Lysosomal Enzymes: Accumulation of Lipofuscin-Like Dense Bodies in the Brain
Ivy, G. O., Schottler, F., Wenzel, J., Baudry, M., & LYNCH, G. S. (1984) · Science · doi:10.1126/science.6505679 · Cited by 269
Cathepsins B and D are dispensable for major histocompatibility complex class II-mediated antigen presentation
Deussing, J. M., Roth, W., Säftig, P., Peters, C., Ploegh, H. L., & Villadangos, J. A. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.8.4516 · Cited by 266
Self-citation
A mutation in the ovine cathepsin D gene causes a congenital lysosomal storage disease with profound neurodegeneration
Tyynelä, J., Sohar, I., Sleat, D. E., Gin, R. M., Donnelly, R. J., Baumann, M., Haltia, M., & Lobel, P. (2000) · The EMBO Journal · doi:10.1093/emboj/19.12.2786 · Cited by 245
Cathepsin S Controls the Trafficking and Maturation of Mhc Class II Molecules in Dendritic Cells
Driessen, C., Bryant, R. A. R., Lennon‐Duménil, A., Villadangos, J. A., Wolf, P. R., Shi, G., Chapman, H. A., & Ploegh, H. L. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.147.4.775 · Cited by 231
Self-citation
Selective targeting of lysosomal cysteine proteases with radiolabeled electrophilic substrate analogs
Bogyo, M. S., Verhelst, S. H. L., Bellingard, V., Toba, S., & Greenbaum, D. C. (2000) · Chemistry & Biology · doi:10.1016/s1074-5521(00)00061-2 · Cited by 217
Extensive trafficking of MHC class II-invariant chain complexes in the endocytic pathway and appearance of peptide-loaded class II in multiple compartments
Castellino, F., & Germain, R. N. (1995) · Immunity · doi:10.1016/1074-7613(95)90080-2 · Cited by 194
Processing of human cathepsin D in lysosomes in vitro.
Gieselmann, V., Hasilík, A., & FIGURA, K. V. (1985) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)89493-5 · Cited by 157
Classical late infantile neuronal ceroid lipofuscinosis fibroblasts are deficient in lysosomal tripeptidyl peptidase I1
Vines, D. J., & Warburton, M. J. (1999) · FEBS Letters · doi:10.1016/s0014-5793(98)01683-4 · Cited by 152
Regulation of a novel pathway for cell death by lysosomal aspartic and cysteine proteinases
Isahara, K., Ohsawa, Y., Kanamori, S., Shibata, M., Waguri, S., Sato, N., Gotow, T., Watanabe, T., Momoi, T., Urase, K., et al. (1999) · Neuroscience · doi:10.1016/s0306-4522(98)00566-1 · Cited by 149
The Neuronal Ceroid Lipofuscinoses (Batten Disease),
Koeppen, A. H. (2000) · Journal of the Neurological Sciences · doi:10.1016/s0022-510x(00)00289-6 · Cited by 137
Specific Storage of Subunit c of Mitochondrial ATP Synthase in Lysosomes of Neuronal Ceroid Lipofuscinosis (Batten's Disease)1
Kominami, E., Ezaki, J., Muno, D., Ishido, K., Ueno, T., & Wolfe, L. S. (1992) · The Journal of Biochemistry · doi:10.1093/oxfordjournals.jbchem.a123749 · Cited by 119
A Rapid Fluorogenic Palmitoyl-Protein Thioesterase Assay: Pre- and Postnatal Diagnosis of INCL
van Diggelen, O. P., Keulemans, J. L. M., WINCHESTER, B. G., Hofman, I. L., Vanhanen, S.-L., Santavuori, P., & Voznyi, Y. V. (1999) · Molecular Genetics and Metabolism · doi:10.1006/mgme.1999.2809 · Cited by 118
Cathepsin B Expression in Human Tumors
Berquin, I. M., & Sloane, B. F. (1996) · Advances in experimental medicine and biology · doi:10.1007/978-1-4613-0335-0_35 · Cited by 106
Suppression of Cathepsins B and L Causes a Proliferation of Lysosomes and the Formation of Meganeurites in Hippocampus
Bednarski, E., Ribak, C. E., & LYNCH, G. S. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-11-04006.1997 · Cited by 82
On the degradability and exocytosis of ceroid/lipofuscin in cultured rat cardiac myocytes
Terman, A., & Brunk, U. T. (1998) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(97)00129-2 · Cited by 80
The possible place of cathepsins and cystatins in the puzzle of Alzheimer disease
Bernstein, H., Kirschke, H., Wiederanders, B., Kh, P., Zipress, A., & Rinne, A. (1996) · Molecular and Chemical Neuropathology · doi:10.1007/bf02815106 · Cited by 70
Cathepsin expression during skeletal development
Söderström, M., Salminen, H., Glumoff, V., Kirschke, H., Aro, H. T., & VUORIO, E. I. (1999) · Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression · doi:10.1016/s0167-4781(99)00068-8 · Cited by 68
Syndrome of coronal craniosynostosis with brachydactyly and carpal/tarsal coalition due to Pro250Arg mutation in FGFR3 gene.
Graham, J. M., Braddock, S. R., Mortier, G., Lachman, R., van Dop, C., & Jabs, E. (1998) · American journal of medical genetics · doi:10.1002/(sici)1096-8628(19980526)77:4 · Cited by 62
Enzyme-based Diagnosis of Classical Late Infantile Neuronal Ceroid Lipofuscinosis: Comparison of Tripeptidyl Peptidase I and Pepstatin-insensitive Protease Assays
Sohár, I., Lin, L., & Lobel, P. (2000) · Clinical Chemistry · doi:10.1093/clinchem/46.7.1005 · Cited by 62
Differential distribution of messenger RNAs for cathepsins B, L and S in adult rat brain: An in situ hybridization study
Petanceska, S. S., Burke, S., Watson, S. J., & Devi, L. A. (1994) · Neuroscience · doi:10.1016/0306-4522(94)90190-2 · Cited by 61
Two related proteolipids and dolichol-linked oligosaccharides accumulate in motor neuron degeneration mice (mnd/mnd), a model for neuronal ceroid lipofuscinosis
Faust, J. R., Rodman, J. S., Daniel, P., Dice, J. F., & Bronson, R. T. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)37002-3 · Cited by 59
Self-citation
Identification of an enzyme in human kidney that correctly processes prorenin.
Shinagawa, T., Do, Y. S., Baxter, J. D., Carilli, C. T., Schilling, J., & Hsueh, W. A. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.5.1927 · Cited by 49
Thirty Years of Batten Disease Research: Present Status and Future Goals
Rider, J. A., & Rider, D. L. (1999) · Molecular Genetics and Metabolism · doi:10.1006/mgme.1999.2827 · Cited by 26
Fine structure of cutaneous nerves in ganglioside storage disease.
Dolman, C. L., MacLeod, P., & Chang, E. (1977) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.40.6.588 · Cited by 22
Ultrastructural pathology of dermal axons and Schwann cells in lysosomal diseases
Walter, S., & Goebel, H. H. (1988) · Acta Neuropathologica · doi:10.1007/bf00686388 · Cited by 20
Self-citation
Lysosomal Dysfunction Results in Lamina-Specific Meganeurite Formation but Not Apoptosis in Frontal Cortex
Yong, A. P., Bednarski, E., Gall, C. M., LYNCH, G. S., & Ribak, C. E. (1999) · Experimental Neurology · doi:10.1006/exnr.1999.7038 · Cited by 18

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).

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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)
ORCID: Felbor, Ute
Kessler, Benedikt
Mothes, Walther
Goebel, Hans H.
Ploegh, Hidde L.
Bronson, Roderick T.
Olsen, Bjorn R.
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
DOI: 10.1073/pnas.112632299
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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Neuronal loss and brain atrophy in mice lacking cathepsins B and L

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