Skip to main content
SpringerLink
Log in
Book cover

Pathophysiological Aspects of Proteases pp 147–160Cite as

Tripeptidyl Peptidase I and Its Role in Neurodegenerative and Tumor Diseases

  • Chapter
  • First Online:

Abstract

Tripeptidyl peptidase I (TPPI) is a lysosomal enzyme widely distributed in mammals and humans. Its genetically determined deficiency causes the classical late-infantile form of neuronal ceroid lipofuscinosis, a fatal hereditary neurodegenerative disease associated with severe symptoms and early death, usually in the second decade of life. Many studies also show that TPPI is differentially regulated under various pathological conditions such as malignancy, neurodegeneration, ischemia, and inflammation, pointing at possible enzyme involvement in the pathogeneses of these entities. This chapter focuses on the TPPI participation in neurodegenerative and neoplastic diseases.

This is a preview of subscription content, log in via an institution.

References

  1. Page AE, Fuller K, Chambers TJ, Warburton MJ (1993) Purification and characterization of a tripeptidyl peptidase I from human osteoclastomas: evidence for its role in bone resorption. Arch Biochem Biophys 306:354–359

    Article  CAS  Google Scholar 

  2. Vines D, Varburton MJ (1998) Purification and characterisation of a tripeptidyl aminopeptidase I from rat spleen. Biochim Biophys Acta 1384:233–242

    Article  CAS  Google Scholar 

  3. Ezaki J, Takeda-Ezaki M, Oda K, Kominami E (2000) Characterization of endopeptidase activity of tripeptidyl peptidase-I/CLN2 protein which is deficient in classical late infantile neuronal ceroid lipofuscinosis. J Biochem Biophys Res Commun 268:904–908

    Article  CAS  Google Scholar 

  4. Kondo MY, Gouvea IE, Okamoto DN, Santos JAN, Souccar C, Oda K, Juliano L, Juliano MA (2016) Analysis of catalytic properties of tripeptidyl peptidase I (TTP-I), a serine carboxyl lysosomal protease, and its detection in tissue extracts using selective FRET peptide substrate. Peptides 76:80–86

    Article  CAS  Google Scholar 

  5. Wlodawer A, Li M, Gustchina A, Oyama H, Dunn BM, Oda K (2003) Structural and enzymatic properties of the sedolisin family of serine-carboxyl peptidases. Acta Biochim Polon 50:81–102

    CAS  PubMed  Google Scholar 

  6. Oda K (2012) New families of carboxyl peptidases: serine-carboxyl peptidases and glutamic peptidases. J Biochem 151:13–25

    Article  CAS  Google Scholar 

  7. Sharp JD, Wheeler RB, Lake BD, Savukoski M, Jarvela IE, Peltonen L, Gardiner RM, Williams RE (1997) Hum Mol Genet 6:591–595

    Article  CAS  Google Scholar 

  8. Sleat DE, Donnelly JR, Lackland H, Lin GC, Sohar I, Pullarkat RK, Lobel P (1997) Association of mutations in a lysosomal protein with classical late-infantile neuronal ceroid lipofuscinosis. Science 277:1802–1805

    Article  CAS  Google Scholar 

  9. Lin L, Sohar I, Lackland H, Lobel P (2001) The human CLN2 protein/tripeptidyl peptidase I is a serine protease that autoactivates at acidic pH. J Biol Chem 276:2249–2255

    Article  CAS  Google Scholar 

  10. Golabek A, Kida E, Walus M, Wujek P, Mentha P, Wisniewski K (2003) Human tripeptidyl-peptidase I: biosynthesis, glycosylation and enzymatic processing in vivo. J Biol Chem 278:7135–7145

    Article  CAS  Google Scholar 

  11. Golabek A, Wujek P, Walus M, Bieler S, Soto C, Wisniewski K, Kida E (2004) Maturation of human tripeptidyl-peptidase I in vitro. J Biol Chem 279:31058–31067

    Article  CAS  Google Scholar 

  12. Wujek P, Kida E, Walus M, Wisniewski K, Golabek A (2004) N-glycosylation is crucial for folding, trafficking, and stability of human tripeptidyl-peptidase I. J Biol Chem 279:12827–12839

    Article  CAS  Google Scholar 

  13. Walus M, Kida E, Wisniewski K, Golabek A (2005) Ser475, Glu272, Asp276, Asp327 and Asp360 are involved in catalytic activity of human tripeptidyl-peptydase I. FEBS Lett 579:1383–1388

    Article  CAS  Google Scholar 

  14. Kuizon S, DiMaiuta K, Walus M, Jenkins EC Jr, Kuizon M, Kida E, Golabek AA, Espinoza DO, Pullarkat RK, Junaid MA (2010) A critical tryptophan and Ca2+ in activation and catalysis of TPPI, the enzyme deficient in classic late-infantile neuronal ceroid lipofuscinosis. PLoS ONE 5(8):e11929

    Article  Google Scholar 

  15. Pal A, Kraetzner R, Gruene T, Grapp M, Schreiber K, Groenborg M, Urlaub H, Becker S, Asif AR, Gaertner J, Sheldrick GM, Steinfeld R (2009) Structure of tripeptidyl-peptidase I provides insight into the molecular basis of late infantile neuronal ceroid lipofuscinosis. J Biol Chem 284:3976–3984

    Article  CAS  Google Scholar 

  16. Guhaniyogi J, Sohar I, Das K, Stock A, Lobel P (2009) Crystal structure and autoactivation pathway of the precursor form of human tripeptidyl-peptidase I, the enzyme deficient in late infantile ceroid lipofuscinosis. J Biol Chem 284:3985–3997

    Article  CAS  Google Scholar 

  17. Tsiakas K, Steinfeld R, Storch S, Ezaki J, Lukacs Z, Kominami E, Kohlschutter A, Ullrich K, Braulke T (2004) Mutation of the glycosylated asparagines residue 286 in human CLN2 protein results in loss of enzymatic activity. Glycobiology 14:1C–5C

    Article  CAS  Google Scholar 

  18. Golabek AA, Dolzhanskaya N, Walus M, Wisniewski KE, Kida E (2008) Prosegment of tripeptidyl peptidase I is a potent, slow-binding inhibitor of its cognate enzyme. J Biol Chem 283:16497–16504

    Article  CAS  Google Scholar 

  19. Junaid M, Wu G, Pullarkat R (2000) Purification and characterization of bovine brain lysosomal pepstatin-insensitive proteinase, the gene product deficient in the human late-infantile neuronal ceroid lipofuscinosis. J Neurochem 74:287–294

    Article  CAS  Google Scholar 

  20. Tian Y, Sohar I, Taylor JW, Lobel P (2006) Determination of the substrate specificity of tripeptidyl-peptidase I using combinatorial peptide libraries and development of improved fluorogenic substrates. J Biol Chem 281:6559–6572

    Article  CAS  Google Scholar 

  21. Dikov A, Dimitrova M, Ivanov I, Krieg R, Halbhuber K-J (2000) Original method for the histochemical demonstration of tripeptidyl aminopeptidase I. Cell Mol Biol 46:1219–1225

    CAS  PubMed  Google Scholar 

  22. Steinfeld R, Fuhrmann J, Gartner J (2006) Detection of tripeptidyl peptidase I activity in living cells by fluorogenic substrates. J Histochem Cytochem 54:991–996

    Article  CAS  Google Scholar 

  23. Ivanov I, Tascheva D, Todorova R, Dimitrova M (2009) Synthesis and use of 4-peptidylhydrazido-N-hexyl-1,8-naphthalimides as fluorogenic histochemical substrates for dipeptidyl peptidase IV and tripeptidyl peptidase I. Eur J Med Chem 44:384–392

    Article  CAS  Google Scholar 

  24. Bernardini F, Warburton M (2002) Lysosomal degradation of cholecystokinin-(29–33)-amide in mouse brain is dependent of tripeptidyl peptidase—I: implications for the degradation and storage of peptides in classical late-infantile neuronal ceroid lipofuscinosis. Biochem J 366:521–529

    Article  CAS  Google Scholar 

  25. Warburton MJ, Bernardini F (2002) Tripeptidyl peptidase-I is essential for the degradation of sulphated cholecystokinin-8 (CCK-8S) by mouse brain lysosomes. Neurosci Lett 331:99–102

    Article  CAS  Google Scholar 

  26. Du P, Kato S, Li Y, Maeda T, Yamane T, Yamamoto S, Fujiwara, Yamamoto Y, Nishi K, Ohkubo I (2001) Rat tripeptidyl peptidase I: molecular cloning, functional expression, tissue localization and enzymatic characterization. Biol Chem 382:1715–1725

    Google Scholar 

  27. Kopan S, Sivasubramaniam U, Warburton M (2004) The lysosomal degradation of neuromedin B is dependent on tripeptydil peptidase—I: evidence for the impairment of neuropeptide degradation in late-infantile neuronal ceroid lipofuscinosis. Biochem Biophys Res Commun 319:58–65

    Article  CAS  Google Scholar 

  28. Ezaki J, Tanida I, Kanehagi N, Kominami E (1999) A lysosomal proteinase, the late infantile neuronal ceroid lipofuscinosis gene (CLN2) product, is essential for degradation of a hydrophobic protein, the subunit c of ATP synthase. J Neurochem 72:2573–2582

    Article  CAS  Google Scholar 

  29. Wlodawer A, Durell SR, Li M, Oyama H, Oda K, Dunn B (2003) A model of tripeptidyl peptidase I (CLN2), a ubiquitous and highly conserved member of the sedolisin family of serine-carboxyl peptidases. BMC Struct Biol 3:8–18

    Article  Google Scholar 

  30. Koike M, Shibata M, Ohsawa Y, Kametaka S, Waguri S, Kominami E, Uchiyama Y (2002) The expression of trypeptidyl peptidase I in various tissues of rats and mice. Arch Histol Cytol 65:219–232

    Article  CAS  Google Scholar 

  31. Dimitrova M, Ivanov I, Deleva D (2009) Distribution of tripeptidyl peptidase I activity in the rat brain and spinal cord. Comp Rend Acad Bulg Sci 62:729–734

    CAS  Google Scholar 

  32. Dimitrova M, Deleva D (2009) Histochemical study of the changes in trypeptidyl peptidase I activity in developing rat brain and spinal cord. Compt Rend Acad Bulg Sci 62:1407–1412

    CAS  Google Scholar 

  33. Yayoi Y, Ohsawa Y, Koike M, Zhang GQ, Kominami E, Uchiyama Y (2001) Specific localization of lysosomal aminopeptidases in type II alveolar epithelial cells of the rat lung. Arch Histol Cytol 64:89–97

    Article  CAS  Google Scholar 

  34. Dimitrova M, Ivanov I, Todorova R, Tsenova V (2008) Fluorescent localization of tripeptidyl peptidase I activity in tissue sections of Balb/c mice reproductive organs. Compt Rend Acad Bulg Sci 61:349–356

    CAS  Google Scholar 

  35. Atanasova D, Lazarov N (2015) Histochemical demonstration of tripeptidyl aminopeptidase I in the rat carotid body. Acta Histochem 117:219–222

    Article  CAS  Google Scholar 

  36. Kurachi Y, Oka A, Itoh M, Mizuguchi M, Hayashi M, Takashima S (2001) Distribution and development of CLN-2 protein, the late-infantile neuronal ceroid lipofuscinosis gene product. Acta Neuropathol 102:20–26

    CAS  PubMed  Google Scholar 

  37. Kida E, Golabek A, Walus M, Wujek P, Kaczmarski W, Wisniewski EK (2001) Distribution of tripeptidyl peptidase I in human tissues under normal and pathological conditions. J Neuropathol Exper Neurol 60:280–292

    Article  CAS  Google Scholar 

  38. Suopanki J, Partanen S, Ezaki J, Baumann M, Kominami E, Tyynela J (2000) Developmental changes in the expression of neuronal ceroid lipofuscinoses-linked proteins. Mol Genet Metab 71:190–194

    Article  CAS  Google Scholar 

  39. Dimitrova M, Deleva D, Pavlova V, Ivanov I (2011) Developmental study of tripeptidyl peptidase I activity in the mouse central nervous system and peripheral organs. Cell Tissue Res 346:141–149

    Article  CAS  Google Scholar 

  40. Autefage H, Albinet V, Garcia V, Berges H, Nicolau ML, Therville N, Altie MF, Caillaud C, Levade T, Andrieu-Abadie N (2009) Lysosomal serine protease CLN2 regulates tumor necrosis factor-alfa-mediated apoptosis in a bid-dependent manner. J Biol Chem 284:11507–11516

    Article  CAS  Google Scholar 

  41. Van Beersel G, Tihon E, Demine S, Hamer I, Jadot M, Arnould T (2013) Different molecular mechanisms involved in spontaneous and oxidative stress-induced mitochondrial fragmentation in tripeptidyl peptidase-1 (TPP-1)-deficient fibroblasts. Biosci Rep 33:243–258

    Google Scholar 

  42. Golabek AA, Kida E (2006) Tripeptidyl-peptidase I in health and disease. Biol Chem 387:1091–1099

    Article  CAS  Google Scholar 

  43. Marani E, Lazarov N (2016) Lipofuscin and lipofuscinosis. Neuroscience and Biobehavioral Psychology. Elsevier, Nr. 02594 (in press)

    Google Scholar 

  44. Williams RE, Mole SE (2012) New nomenclature and classification scheme for the neuronal ceroid lipofuscinoses. Neurology 79:183–191

    Article  Google Scholar 

  45. Kousi M, Lehesjoki AE, Mole SE (2012) Update of the mutation spectrum and clinical correlations of over 360 mutations in eight genes that underlie the neuronal ceroid lipofuscinoses. Hum Mutat 33:42–63

    Article  CAS  Google Scholar 

  46. Mole SE, Williams RE, Goebel HH (2011) The neuronal ceroid lipofuscinoses (Batten disease), contemporary neurology series. Oxford University Press, Oxford, p 480

    Google Scholar 

  47. Wisniewski KE, Kida E, Connell F, Zhong N (2000) Neuronal ceroid lipofuscinoses: research update. Neurol Sci 21:S49–S56

    Article  CAS  Google Scholar 

  48. Wisniewski KE, Kida E, Golabek AA, Kaszmarski W, Connell F, Zhong N (2001) Neuronal ceroid lipofuscinoses: classification and diagnosis. Adv Genet 45:1–34

    CAS  PubMed  Google Scholar 

  49. Mole SE, Williams RE, Goebel HH (2005) Correlations between genotype, ultrastructural morphology and clinical phenotype in the neuronal ceroid lipofuscinoses. Neurogenetics 6:107–126

    Article  Google Scholar 

  50. Williams RE, Aberg L, Autti T, Goebel HH, Kohlschütter A, Lönnqvist T (2006) Diagnosis of the neuronal ceroid lipofuscinoses: an update. Biochim Biophys Acta 1762:865–872

    Article  CAS  Google Scholar 

  51. Persaud-Sawin D-A, Mousallem T, Wang C, Zucker A, Kominami E Boustany R-MN (2007) Neuronal ceroid lipofuscinosis: a common pathway? Pediatric Res 61:146–152

    Article  Google Scholar 

  52. Pierret C, Morrison JA, Kirk MD (2008) Treatment of lysosomal storage disorders: focus on the neuronal ceroid-lipofuscinoses. Acta Neurobiol Exp 68(429):442

    Google Scholar 

  53. Getty AL, Pearce DA (2011) Interactions of the proteins of neuronal ceroid lipofuscinosis: clues to function. Cell Mol Life Sci 68:453–474

    Article  CAS  Google Scholar 

  54. Warrier V, Vieira M, Mole SE (2013) Genetic basis and phenotypic correlations of the neuronal ceroid lipofuscinoses. Biochim Biophys Acta 1832:1827–1830

    Article  CAS  Google Scholar 

  55. Kohan R, Mole SE, Cotman SL (eds) (2015) Current research on the neuronal ceroid lipofuscinoses (Batten disease). Biochim Biophys Acta (BBA)—Mol Basis Dis 1852(10),Part B:2235–2338

    Google Scholar 

  56. Steinfeld R, Heim P, von Gregory H, Meyer K, Ullrich K, Goebel HH, Kohlschutter A (2002) Late infantile neuronal ceroid lipofuscinosis: quantitative description of the clinical course in patients with CLN2 mutations. Am J Med Genet 112:347–354

    Article  Google Scholar 

  57. Steinfeld R, Steinke H-B, Isbrandt D, Kohlschuaetter A, Gaertner J (2004) Mutations in classical late infantile neuronal ceroid lipofuscinosis disrupt transport of tripeptidyl-peptidase I to lysosomes. Hum Mol Genet 13:2483–2491

    Article  CAS  Google Scholar 

  58. Kohan R, Carabelos MN, Xin W, Sims K, Guelbert N, Cismondi IA, Pons P, Alonso GI, Troncoso M, Witting S, Pearce DA, Dodelson de Kremer R, Oller-Ramírez AM, Noher de Halac I (2013) Neuronal ceroid lipofuscinosis type CLN2: a new rationale for the construction of phenotypic subgroups based on a survey of 25 cases in South America. Gene 516:114–121

    Article  CAS  Google Scholar 

  59. Sleat DE, El-Banna M, Sohar I, Kim K-H, Dobrenis K, Walkley SU, Lobel P (2008) Residual levels of tripeptidyl-peptidase I activity dramatically ameliorate disease in late-infantile neuronal ceroid lipofuscinosis. Mol Genet Metab 94:222–233

    Article  CAS  Google Scholar 

  60. Palmer DN, Oswald MJ, Westlake VJ, Kay GW (2002) The origin of fluorescence in the neuronal ceroid lipofuscinoses (Batten disease) and neuron cultures from affected sheep for studies of neurodegeneration. Arch Gerontol Geriatr 34:343–357

    Article  CAS  Google Scholar 

  61. Bond M, Holthaus S-M, Tammen I, Tear G, Russell C (2013) Use of model organisms for the study of neuronal ceroid lipofuscinosis. Biochim Biophys Acta 1832:1842–1865

    Article  CAS  Google Scholar 

  62. Sleat DE, Wiseman JA, El-Banna M, Kim KH, Mao Q, Price S, Macauley SL, Sidman RL, Shen M, Zhao Q, Passini MA, Davidson BL, Stewart GR, Lobel P (2004) A mouse model of classical late-infantile neuronal ceroid lipofuscinosis based on targeted disruption of the CLN2 gene results in a loss of tripeptidylpeptidase I activity and progressive neurodegeneration. J Neurosci 24:9117–9126

    Article  CAS  Google Scholar 

  63. Chang M, Cooper JD, Sleat DE, Cheng SH, Dodge JC, Passini MA, Lobel P, Davidson BL (2008) Intraventricular enzyme replacement improves disease phenotypes in a mouse model of late infantile neuronal ceroid lipofuscinosis. Mol Ther 16:649–656

    Article  CAS  Google Scholar 

  64. Xu S, Wang L, El-Banna M, Sohar I, Sleat DE, Lobel P (2011) Large-volume intrathecal enzyme delivery increases survival of a mouse model of late infantile neuronal ceroid lipofuscinosis. Mol Ther 19:1842–1848

    Article  CAS  Google Scholar 

  65. Passini M, Dodge J, Bu J, Yang W, Zhao Q, Sondhi D, Hackett N, Kaminsky S, Mao Q, Shihabuddin L, Cheng S, Sleat D, Stewart G, Davidson B, Lobel P, Crystal R (2006) Intracranial delivery of CLN2 reduces brain pathology in a mouse model of classical late infantile neuronal ceroid lipofuscinosis. J Neurosci 26:1334–1342

    Article  CAS  Google Scholar 

  66. Sondhi D, Hackett NR, Peterson DA, Stratton J, Baad M, Travis KM, Wilson JM, Crystal RG (2007) Enhanced survival of the LINCL mouse following CLN2 gene transfer using the rh. 10 rhesus macaque-derived adeno-associated virus vector. Mol Ther 15:481–491

    Article  CAS  Google Scholar 

  67. Neverman NJ, Best HL, Hofmann SL, Hughes SM (2015) Experimental therapies in the neuronal ceroid lipofuscinoses. Biochim Biophys Acta 1852:2292–2300

    Article  CAS  Google Scholar 

  68. Zhong NA, Moroziewicz DN, Ju W, Wisniewski KE, Jurkiewicz A, Brown WT (2000) CLN-encoded proteins do not interact with each other. Neurogenetics 3:41–44

    CAS  PubMed  Google Scholar 

  69. Vesa J, Chin MH, Oelgeschlaeger K, Isosomppi J, DellAngelica EC, Jalanko A, Peltonen L (2002) Neuronal ceroid lipofuscinoses are connected at molecular level: interaction of CLN5 protein with CLN2 and CLN3. Mol Biol Cell 13:2410–2420

    Article  CAS  Google Scholar 

  70. Lyly A, von Schantz C, Heine C, Schmiedt ML, Sipilae T, Jalanko A, Kyttaelae A (2009) Novel interactions of CLN5 support molecular networking between neuronal ceroid lipofuscinosis proteins. BMC Cell Biol 10:83

    Article  Google Scholar 

  71. Junaid MA, Pullarkat RK (1999) Increased brain lysosomal pepstatin-insensitive proteinase activity in patients with neurodegenerative diseases. Neurosci Lett 264:157–160

    Article  CAS  Google Scholar 

  72. Breedveld GJ, van Wetten B, Raa GD, Brusse E, van Swieten JC, Oostra BA, Maat-Kievit JA (2004) A new locus for a childhood onset, slowly progressive autosomal recessive spinocerebellar ataxia maps to chromosome 11p15. (Lett) J Med Genet 41:858–866

    Article  CAS  Google Scholar 

  73. Sun Y, Almomani R, Breedveld GJ, Santen GWE, Aten E, Lefeber DJ, Hoff JI, Brusse E, Verheijen FW, Verdijk RM, Kriek M, Oostra B, Breuning MH, Losekoot M, den Dunnen JT, van de Warrenburg BP, Maat-Kievit AJA (2013) Autosomal recessive spinocerebellar ataxia 7 (SCAR7) is caused by variants in TPP1, the gene involved in classic late-infantile neuronal ceroid lipofuscinosis 2 disease (CLN2 disease). Hum Mutat 34:706–713

    Article  CAS  Google Scholar 

  74. Wisniewski KE, Maslinska D, Kitaguchi T, Kim KS, Goebel HH, Haltia M (1990) Topographic heterogeneity of amyloid B-protein epitopes in brains with various forms of neuronal ceroid lipofuscinoses suggesting defective processing of amyloid precursor protein. Acta Neuropathol 1990:26–34

    Article  Google Scholar 

  75. Vidal-Donet JM, Carcel-Trullols J, Casanova B, Aguado C, Knecht E (2013) Alterations in ROS activity and lysosomal pH account for distinct patterns of macroautophagy in LINCL and JNCL fibroblasts. PLoS ONE 8(2):e55526

    Article  CAS  Google Scholar 

  76. Yu WH, Cuervo AM, Kumar A et al (2005) Macroautophagy—a novel beta-amyloid peptide-generating pathway activated in Alzheimer’s disease. J Cell Biol 171:87–98

    Article  CAS  Google Scholar 

  77. Zhong X-P, Wang D, Zhang Y-B, Gui J-F (2009) Identification and characterization of hypoxia-induced genes in Carassius auratus blastulae embryonic cells using suppression subtractive hybridization. Comp Biochem Phys B 152:161–170

    Article  Google Scholar 

  78. Zaidi ZF (2010) Sodium nitrite-induced hypoxic injury in rat hippocampus. Pak J Med Sci 26:532–537

    Google Scholar 

  79. Zaidi ZF (2010) Effects of sodium nitrite-induced hypoxia on cerebellar Purkinje cells in adult rats. Pak J Med Sci 26:261–266

    Google Scholar 

  80. Petrova EB, Dimitrova MB, Ivanov IP, Pavlova VG, Dimitrova SG, Kadiysky DS (2016) Effect of acute hypoxic shock on the rat brain morphology and tripeptidyl peptidase I activity. Acta Histochem 118:496–504

    Article  CAS  Google Scholar 

  81. Junaid MA, Clark GM, Pullarkat RK (2000) A lysosomal pepstatin-insensitive proteinase as a novel biomarker for breast carcinoma. Int J Biol Markers 15:129–134

    Article  CAS  Google Scholar 

  82. Pullarkat RK, Junaid MA (2001) A lysosomal pepstatin-insensitive proteinase as a novel biomarker for detecting and diagnosing breast cancer W02001069260:A2

    Google Scholar 

  83. Altorjay A, Paal B, Sohar N, Kiss J, Szanto I, Sohar I (2005) Significance and prognostic value of lysosomal enzyme activities measured in surgically operated adenocarcinomas of the gastroesophageal junction and squamous cell carcinomas of the lower third of esophagus. World J Gastroenterol 11:5751–5756

    Article  CAS  Google Scholar 

  84. Tsukamato T, Lida J, Dobashi Y, Furukawa T, Konishi F (2006) Overexpression in colorectal carcinoma of two lysosomal enzymes, CLN2 and CLN1, involved in neuronal ceroid lipofuscinosis. Cancer 106:1489–1497

    Article  Google Scholar 

  85. Ioannou YA, Bishop DF, Desnick RJ (1992) Overexpression of human alpha-galactosidase A results in its intracellular aggregation, crystallization in lysosomes, and selective secretion. J Cell Biol 119:1137–1150

    Article  CAS  Google Scholar 

  86. Andrews NW (2002) Lysosomes and the plasma membrane: trypanosomes reveal a secret relationship. J Cell Biol 158:389–394

    Article  CAS  Google Scholar 

  87. Golabek AA, Walus M, Wisniewski KE, Kida E (2005) Glycosaminoglycans modulate activation, activity, and stability of tripeptidyl-peptidase I in vitro and in vivo. J Biol Chem 280:7550–7560

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors would like to thank Dr. Enrico Marani and Dr. Angel Dandov for their helpful comments and critical reading of the manuscript.

Author information

Authors and Affiliations

  1. Institute of Experimental Morphology, Pathology and Anthropology with Museum, Bulgarian Academy of Sciences, 1113, Sofia, Bulgaria

    Mashenka B. Dimitrova

  2. Institute of Neurobiology, Bulgarian Academy of Sciences, 1113, Sofia, Bulgaria

    Dimitrinka Y. Atanasova & Nikolai E. Lazarov

  3. Department of Anatomy and Histology, Faculty of Medicine, Medical University of Sofia, 2, Zdrave Street, 1431, Sofia, Bulgaria

    Nikolai E. Lazarov

  4. Department of Anatomy, Faculty of Medicine, Trakia University, 6003, Stara Zagora, Bulgaria

    Dimitrinka Y. Atanasova

Authors
  1. Mashenka B. Dimitrova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dimitrinka Y. Atanasova
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nikolai E. Lazarov
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nikolai E. Lazarov .

Editor information

Editors and Affiliations

  1. Department of Biochemistry and Biophysics, University of Kalyani, Kalyani, West Bengal, India

    Sajal Chakraborti

  2. Institute of Cardiovascular Sciences, University of Manitoba, Manitoba, Canada

    Naranjan S. Dhalla

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Dimitrova, M.B., Atanasova, D.Y., Lazarov, N.E. (2017). Tripeptidyl Peptidase I and Its Role in Neurodegenerative and Tumor Diseases. In: Chakraborti, S., Dhalla, N. (eds) Pathophysiological Aspects of Proteases. Springer, Singapore. https://doi.org/10.1007/978-981-10-6141-7_6

Download citation

Publish with us

Policies and ethics

Search

Navigation