Cathepsin B

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PDB 1csb EBI.jpg
Available structures
PDB Ortholog search: PDBe RCSB
Aliases CTSB, APPS, CPSB, cathepsin B
External IDs OMIM: 116810 MGI: 88561 HomoloGene: 37550 GeneCards: 1508
RNA expression pattern
PBB GE CTSB 200838 at tn.png

PBB GE CTSB 200839 s at tn.png

PBB GE CTSB 213274 s at tn.png
More reference expression data
Species Human Mouse
RefSeq (mRNA)


RefSeq (protein)



Location (UCSC) Chr 8: 11.84 – 11.87 Mb Chr 14: 63.12 – 63.15 Mb
PubMed search [1] [2]
View/Edit Human View/Edit Mouse

Cathepsin B (CatB) is an enzymatic protein belonging to the peptidase (or protease) families. In humans, it is coded by the CTSB gene.[1][2]


The protein encoded by this gene is a lysosomal cysteine protease composed of a dimer of disulfide-linked heavy and light chains, both produced from a single protein precursor. It is a member of the peptidase C1 family. At least five transcript variants encoding the same protein have been found for this gene.[3]

Clinical significance[edit]

Cathepsin B is produced in muscle tissue during metabolism.[4] It is capable of crossing the blood-brain barrier[5] and is associated with neurogenesis, specifically in the mouse dentate gyrus.

A wide array of diseases result in elevated levels of cathepsin B, which causes numerous pathological processes including cell death, inflammation, and production of toxic peptides. Focusing on neurological diseases, cathepsin B gene knockout studies in an epileptic rodent model have shown cathepsin B causes a significant amount of the apoptotic cell death that occurs as a result of inducing epilepsy.[6] Cathepsin B inhibitor treatment of rats in which a seizure was induced resulted in improved neurological scores, learning ability and much reduced neuronal cell death and pro-apoptotic cell death peptides.[7] Similarly, cathepsin B gene knockout and cathepsin B inhibitor treatment studies in traumatic brain injury mouse models have shown cathepsin B to be key to causing the resulting neuromuscular dysfunction, memory loss, neuronal cell death and increased production of pro-necrotic and pro-apoptotic cell death peptides.[8][9] In ischemic non-human primate and rodent models, cathepsin B inhibitor treatment prevented a significant loss of brain neurons, especially in the hippocampus.[10][11][12] In a streptococcus pneumoniae meningitis rodent model, cathepsin B inhibitor treatment greatly improved the clinical course of the infection and reduced brain inflammation and inflammatory Interleukin-1beta (IL1-beta) and tumor necrosis factor-alpha (TNFalpha).[13] In a transgenic Alzheimer's disease (AD) animal model expressing human amyloid precursor protein (APP) containing the wild-type beta-secretase site sequence found in most AD patients or in guinea pigs, which are a natural model of human wild-type APP processing, genetically deleting the cathepsin B gene or chemically inhibiting cathepsin B brain activity resulted in a significant improvement in the memory deficits that develop in such mice and reduces levels of neurotoxic full-length Abeta(1-40/42) and the particularly pernicious pyroglutamate Abeta(3-40/42), which are thought to cause the disease.[14][15][16][17][18][19][20] In a non-transgenic senescence-accelerated mouse strain, which also has APP containing the wild-type beta-secretase site sequence, treatment with bilobalide, which is an extract of Ginko biloba leaves, also lowered brain Abeta by inhibiting cathepsin B.[21] Moreover, siRNA silencing or chemically inhibiting cathepsin B in primary rodent hippocampal cells or bovine chromaffin cells, which have human wild-type beta-secretase activity, reduces secretion of Abeta by the regulated secretory pathway.[22][23]

Mutations in the CTSB gene have been linked to tropical pancreatitis, a form of chronic pancreatitis.[24]


Cathepsin B has been shown to interact with:

See also[edit]


  1. ^ Chan SJ, San Segundo B, McCormick MB, Steiner DF (October 1986). "Nucleotide and predicted amino acid sequences of cloned human and mouse preprocathepsin B cDNAs". Proc. Natl. Acad. Sci. U.S.A. 83 (20): 7721–5. doi:10.1073/pnas.83.20.7721. PMC 386793. PMID 3463996. 
  2. ^ Cao L, Taggart RT, Berquin IM, Moin K, Fong D, Sloane BF (February 1994). "Human gastric adenocarcinoma cathepsin B: isolation and sequencing of full-length cDNAs and polymorphisms of the gene". Gene 139 (2): 163–9. doi:10.1016/0378-1119(94)90750-1. PMID 8112600. 
  3. ^ "Entrez Gene: CTSB cathepsin B". 
  4. ^ Vivar, Carmen; Potter, Michelle C.; van Praag, Henriette (2012). "All About Running: Synaptic Plasticity, Growth Factors and Adult Hippocampal Neurogenesis" 15: 189–210. doi:10.1007/7854_2012_220. ISSN 1866-3370. 
  5. ^ Moon, Hyo Youl; Becke, Andreas; Berron, David; Becker, Benjamin; Sah, Nirnath; Benoni, Galit; Janke, Emma; Lubejko, Susan T.; Greig, Nigel H.; Mattison, Julie A.; Duzel, Emrah; van Praag, Henriette (2016). "Running-Induced Systemic Cathepsin B Secretion Is Associated with Memory Function". Cell Metabolism. doi:10.1016/j.cmet.2016.05.025. ISSN 1550-4131. 
  6. ^ Houseweart MK, Pennacchio LA, Vilaythong A, Peters C, Noebels JL, Myers RM (2003). "Cathepsin B but not cathepsins L or S contributes to the pathogenesis of Unverricht-Lundborg progressive myoclonus epilepsy (EPM1)". J. Neurobiol. 56 (4): 315–27. doi:10.1002/neu.10253. PMID 12918016. 
  7. ^ Ni H, Ren SY, Zhang LL, Sun Q, Tian T, Feng X (2013). "Expression profiles of hippocampal regenerative sprouting-related genes and their regulation by E-64d in a developmental rat model of penicillin-induced recurrent epilepticus". Toxicol. Lett. 217 (2): 162–9. doi:10.1016/j.toxlet.2012.12.010. PMID 23266720. 
  8. ^ Hook GR, Yu J, Sipes N, Pierschbacher MD, Hook V, Kindy MS (2013). "The Cysteine Protease Cathepsin B is a Key Drug Target and Cysteine Protease Inhibitors are Potential Therapeutics for Traumatic Brain Injury". J Neurotrauma 31 (5): 515–29. doi:10.1089/neu.2013.2944. PMC 3934599. PMID 24083575. 
  9. ^ Luo CL, Chen XP, Yang R, Sun YX, Li QQ, Bao HJ, Cao QQ, Ni H, Qin ZH, Tao LY (2010). "Cathepsin B contributes to traumatic brain injury-induced cell death through a mitochondria-mediated apoptotic pathway". J Neurosci Res 88 (13): 2847–58. doi:10.1002/jnr.22453. PMID 20653046. 
  10. ^ Yoshida M, Yamashima T, Zhao L, Tsuchiya K, Kohda Y, Tonchev AB, Matsuda M, Kominami E (2002). "Primate neurons show different vulnerability to transient ischemia and response to cathepsin inhibition". Acta Neuropathol (Berl) 104 (3): 267–72. doi:10.1007/s00401-002-0554-4. PMID 12172912. 
  11. ^ Tsuchiya K, Kohda Y, Yoshida M, Zhao L, Ueno T, Yamashita J, Yoshioka T, Kominami E, Yamashima T (1999). "Postictal blockade of ischemic hippocampal neuronal death in primates using selective cathepsin inhibitors". Exp Neurol 155 (2): 187–94. doi:10.1006/exnr.1998.6988. PMID 10072294. 
  12. ^ Tsubokawa T, Yamaguchi-Okada M, Calvert JW, Solaroglu I, Shimamura N, Yata K, Zhang JH (2006). "Neurovascular and neuronal protection by E64d after focal cerebral ischemia in rats". J Neurosci Res 84 (4): 832–40. doi:10.1002/jnr.20977. PMID 16802320. 
  13. ^ Hoegen T, Tremel N, Klein M, Angele B, Wagner H, Kirschning C, Pfister HW, Fontana A, Hammerschmidt S, Koedel U (2011). "The NLRP3 inflammasome contributes to brain injury in pneumococcal meningitis and is activated through ATP-dependent lysosomal cathepsin B release". J Immunol 187 (10): 5440–51. doi:10.4049/jimmunol.1100790. PMID 22003197. 
  14. ^ Hook VY, Kindy M, Hook G (2008). "Inhibitors of cathepsin B improve memory and reduce Abeta in transgenic Alzheimer's Disease mice expressing the wild-type, but not the Swedish mutant, beta -secretase APP site". J Biol Chem 283 (12): 7745–7753. doi:10.1074/jbc.m708362200. PMID 18184658. 
  15. ^ Hook V, Kindy M, Hook G (2007). "Cysteine protease inhibitors effectively reduce in vivo levels of brain beta-amyloid related to Alzheimer's disease". Biol Chem 388 (2): 247–52. doi:10.1515/bc.2007.027. PMID 17261088. 
  16. ^ Hook G, Hook VY, Kindy M (2007). "Cysteine protease inhibitors reduce brain beta-amyloid and beta-secretase activity in vivo and are potential Alzheimer's disease therapeutics". Biol Chem 388 (9): 979–83. doi:10.1515/BC.2007.117. PMID 17696783. 
  17. ^ Hook VY, Kindy M, Reinheckel T, Peters C, Hook G (2009). "Genetic cathepsin B deficiency reduces beta-amyloid in transgenic mice expressing human wild-type amyloid precursor protein". Biochem Biophys Res Commun 386 (2): 284–8. doi:10.1016/j.bbrc.2009.05.131. PMID 19501042. 
  18. ^ Hook G, Hook V, Kindy M (2011). "The Cysteine Protease Inhibitor, E64d, Reduces Brain Amyloid-beta and Improves Memory Deficits in Alzheimer's Disease Animal Models by Inhibiting Cathepsin B, but not BACE1, beta-Secretase Activity". J Alzheimers Dis 26 (2): 387–408. doi:10.3233/JAD-2011-110101. PMID 21613740. 
  19. ^ Kindy MS, Yu J, Zhu H, El-Amouri SS, Hook V, Hook GR (2012). "Deletion of the Cathepsin B Gene Improves Memory Deficits in a Transgenic Alzheimer's Disease Mouse Model Expressing AbetaPP Containing the Wild-Type beta-Secretase Site Sequence". J Alzheimers Dis 29 (4): 827–40. doi:10.3233/JAD-2012-111604. PMID 22337825. 
  20. ^ Hook G, Yu J, Toneff T, Kindy M, Hook V (2014). "Brain pyroglutamate amyloid-beta is produced by cathepsin B and is reduced by the cysteine protease inhibitor E64d, representing a potential Alzheimer's disease therapeutic". J Alzheimers Dis 41 (1): 129–49. doi:10.3233/JAD-131370. PMID 24595198. 
  21. ^ Shi C, Zheng DD, Wu FM, Liu J, Xu J (2012). "The phosphatidyl inositol 3 kinase-glycogen synthase kinase 3beta pathway mediates bilobalide-induced reduction in amyloid beta-peptide". Neurochem Res 37 (2): 298–306. doi:10.1007/s11064-011-0612-1. PMID 21952928. 
  22. ^ Hook V, Toneff T, Bogyo M, Greenbaum D, Medzihradszky KF, Neveu J, Lane W, Hook G, Reisine T (2005). "Inhibition of cathepsin B reduces β-amyloid production in regulated secretory vesicles of neuronal chromaffin cells: evidence for cathepsin B as a candidate β-secretase of Alzheimer's disease". Biological Chemistry 386 (9): 931–940. doi:10.1515/BC.2005.108. PMID 16164418. 
  23. ^ Klein DM, Felsenstein KM, Brenneman DE (2009). "Cathepsins B and L differentially regulate amyloid precursor protein processing". J Pharmacol Exp Ther 329 (3): 813–21. doi:10.1124/jpet.108.147082. PMID 19064719. 
  24. ^ Tandon RK (January 2007). "Tropical pancreatitis". J. Gastroenterol. 42 (Suppl 17): 141–7. doi:10.1007/s00535-006-1930-y. PMID 17238044. 
  25. ^ a b Pavlova A, Björk I (September 2003). "Grafting of features of cystatins C or B into the N-terminal region or second binding loop of cystatin A (stefin A) substantially enhances inhibition of cysteine proteinases". Biochemistry 42 (38): 11326–33. doi:10.1021/bi030119v. PMID 14503883. 
  26. ^ Estrada S, Nycander M, Hill NJ, Craven CJ, Waltho JP, Björk I (May 1998). "The role of Gly-4 of human cystatin A (stefin A) in the binding of target proteinases. Characterization by kinetic and equilibrium methods of the interactions of cystatin A Gly-4 mutants with papain, cathepsin B, and cathepsin L". Biochemistry 37 (20): 7551–60. doi:10.1021/bi980026r. PMID 9585570. 
  27. ^ Pol E, Björk I (September 2001). "Role of the single cysteine residue, Cys 3, of human and bovine cystatin B (stefin B) in the inhibition of cysteine proteinases". Protein Sci. 10 (9): 1729–38. doi:10.1110/ps.11901. PMC 2253190. PMID 11514663. 
  28. ^ Mai J, Finley RL, Waisman DM, Sloane BF (April 2000). "Human procathepsin B interacts with the annexin II tetramer on the surface of tumor cells". J. Biol. Chem. 275 (17): 12806–12. doi:10.1074/jbc.275.17.12806. PMID 10777578. 

Further reading[edit]

  • Yan S, Sloane BF (2004). "Molecular regulation of human cathepsin B: implication in pathologies". Biol. Chem. 384 (6): 845–54. doi:10.1515/BC.2003.095. PMID 12887051. 

External links[edit]