Skip to main content
SpringerLink
Log in

Regulation of neuronal cell death and differentiation by NGF and IAP family members

  • Conference paper
Advances in Research on Neurodegeneration

  • 318 Accesses

Summary

Nerve growth factor (NGF) and other neurotrophins were identified because of their trophic role for distinct populations of neurons in the peripheral nervous system. We know that neuronal cell death is regulated by a genetically encoded programme, called apoptosis, that is conserved from worms to humans. Dysregulation of this programme is thought to contribute to neurodegenerative diseases which are characterized by the loss of neurons. This article will review recent findings about the motoneuron disease spinal muscular atrophy (SMA). Two closely linked candidate genes for SMA, the SMN (survival motor neuron) gene and the NAIP (neuronal apoptosis inhibitory protein) gene have been reported. The SMN protein forms a complex with several other proteins and this complex containing SMN plays a critical role in the assembly of spliceosomes and in pre-mRNA splicing. NAIP, cIAP1 (inhibitor of apoptosis-1), c-IAP2, X-IAP and survivin comprise the mammalian inhibitor of apoptosis family. Its members can protect mammalian cells from apoptosis induced by a variety of stimuli. Some of the IAP molecules have been shown to interact both with cell signalling molecules and with specific caspases but details concerning their cellular role are only incompletely characterized.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Birnbaum MJ, Clem RJ, Miller LK (1994) An apoptosis-inhibiting gene from a nuclear polyhedrosis virus encoding a polypeptide with Cys/His sequence motifs. J Virol 68: 2521–2528

    PubMed  CAS  Google Scholar 

  • Charroux B, Pellizzoni L, Perkinson RA, Shevchenko A, Mann M, Dreyfuss G (1999) Gemin3: A novel DEAD box protein that interacts with SMN, the spinal muscular atrophy gene product, and is a component of gems. J Cell Biol 147: 1181–1193

    Article  PubMed  CAS  Google Scholar 

  • Chu Z-L, McKinsey TA, Liu L, Gentry JJ, Malim MH, Ballard DW (1997) Suppression of tumor necrosis factor-induced cell death by inhibitor of apoptosis c-IAP2 is under NF-kB control. Proc Natl Acad Sci USA 94: 10057–10062

    Article  PubMed  CAS  Google Scholar 

  • Coovert DD, Le TT, McAndrew PE, Strasswimmer J, Crawford TO, Mendell JR, Coulson SE, Androphy EJ, Prior TW, Burghes AHM (1997) The survival motor neuron protein in spinal muscular atrophy. Hum Mol Genet 6: 1205–1214

    Article  PubMed  CAS  Google Scholar 

  • Crook NE, Clem RJ, Miller LK (1993) An apoptosis-inhibiting baculovirus gene with a zinc finger-like motif. J Virol 67: 2168–2174

    PubMed  CAS  Google Scholar 

  • Deveraux QL, Takahashi R, Salvesen GS, Reed JC (1997) X-linked IAP is a direct inhibitor of cell-death proteases. Nature 388: 300–304

    Article  PubMed  CAS  Google Scholar 

  • Deveraux QL, Roy N, Stennicke HR, Van Arsdale T, Zhou Q, Srinivasula SM, Alnemri ES, Salvesen GS, Reed JC (1998) IAPs block apoptotic events induced by caspase-8 and cytochrome c by direct inhibition of distinct caspases. EMBO J 17: 2215–2223

    Article  PubMed  CAS  Google Scholar 

  • Duckett CS, Nava VE, Gedrich RW, Clem RJ, Van Dongen JL, Gilfillan MC, Shiels H, Hardwick JM, Thompson CB (1996) A conserved family of cellular genes related to the baculovirus iap gene and encoding apoptosis inhibitors. EMBO J 15: 2685–2694

    PubMed  CAS  Google Scholar 

  • Endrizzi M, Huang S, Scharf JM, Kelter A-R, Wirth B, Kunkel LM, Miller W, Dietrich WF (1999) Comparative sequence analysis of the mouse and human Lgnl/SMA interval. Genomics 60: 137–151

    Article  PubMed  CAS  Google Scholar 

  • Fischer U, Liu Q, Dreyfuss G (1997) The SMN-SIP1 complex has an essential role in spliceosomal snRNP biogenesis. Cell 90: 1023–1029

    Article  PubMed  CAS  Google Scholar 

  • Frade JM, Barde YA (1998) Nerve growth factor: two receptors, multiple functions. BioEssays 20: 137–145

    Article  PubMed  CAS  Google Scholar 

  • Glücksmann A (1951) Cell deaths in normal vertebrate ontogeny. Biol Rev 26: 59–86 Greene LA, Kaplan DR (1995) Early events in neurotrophin signalling via Trk and p75 receptors. Curr Opin Neurobiol 5: 59–86

    Google Scholar 

  • Hawkins CJ, Uren AG, Häcker G, Medcalf RL, Vaux DL (1996) Inhibition of interleukin lb-converting enzyme-mediated apoptosis of mammalian cells by baculovirus IAP. Proc Natl Acad Sci USA 93: 13786–13790

    Article  PubMed  CAS  Google Scholar 

  • Hay BA, Wassarman DA, Rubin GM (1995) Drosophila homologs of baculovirus inhibi-tor of apoptosis proteins function to block cell death. Cell 83: 1253–1262

    Article  PubMed  CAS  Google Scholar 

  • Hengartner MO, Horvitz HR (1994) C. elegans cell survival gene ced-9 encodes a func-tional homolog of the mammalian proto-oncogene bc1–2. Cell 76: 1–2

    Article  PubMed  CAS  Google Scholar 

  • Hengartner MO, Ellis RE, Horvitz HR (1992) Caenorhabditis elegans gene ced-9 pro-tects cells from programmed cell death. Nature 356: 494–499

    Article  PubMed  CAS  Google Scholar 

  • Hsieh-Li HM, Chang JG, Jong YJ, Wu MH, Wang NM, Tsai CH, Li H (2000) A mouse model for spinal muscular atrophy. Nat Genet 24: 66–70

    Article  PubMed  CAS  Google Scholar 

  • Jacobson MD, Weil M, Raff MC (1997) Programmed cell death in animal development. Cell 88: 347–354

    Article  PubMed  CAS  Google Scholar 

  • Kaplan DR, Miller FD (1997) Signal transduction by the neurotrophin receptors. Curr Opin Cell Biol 9: 213–221

    Article  PubMed  CAS  Google Scholar 

  • Kouroku Y, Urase K, Fujita E, Isahara K, Ohsawa Y, Uchiyama Y, Momoi MY, Momoi T (1998) Detection of activated Caspase-3 by a cleavage site-directed antiserum during naturally occurring DRG neurons apoptosis. Biochem Biophys Res Commun 247: 780–784

    Article  PubMed  CAS  Google Scholar 

  • Lazebnik YA, Kaufmann SH, Desnoyers S, Poirier GG, Earnshaw WC (1994) Cleavage of poly(ADP-ribose) polymerase by a proteinase with properties like ICE. Nature 371: 346–347

    Article  PubMed  CAS  Google Scholar 

  • Lefebvre S, Bürglen L, Reboullet S, Clermont O, Burlet P, Viollet L, Benichou B, Cruaud C, Millasseau P, Zeviani M, Le Paslier D, Frézal J, Cohen D, Weissenbach J, Munnich A, Melki J (1995) Identification and characterization of a spinal muscular atrophy-determining gene. Cell 80: 155–165

    Article  PubMed  CAS  Google Scholar 

  • Lefebvre S, Burlet P, Liu Q, Bertrandy S, Clermont O, Munnich A, Dreyfuss G, Melki J (1997) Correlation between severity and SMN protein level in spinal muscular atrophy. Nat Genet 16: 265–269

    Article  PubMed  CAS  Google Scholar 

  • Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES, Wang XD (1997) Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 91: 479–489

    Article  PubMed  CAS  Google Scholar 

  • Liston P, Roy N, Tamai K, Lefebvre C, Baird S, Cherton-Horvat G, Farahani R, McLean M, Ikeda JE, MacKenzie A, Korneluk RG (1996) Suppression of apoptosis in mammalian cells by NAIP and a related family of IAP genes. Nature 379: 349–353

    Article  PubMed  CAS  Google Scholar 

  • Liu Q, Dreyfuss G (1996) A novel nuclear structure containing the survival of motor neurons protein. EMBO J 15: 3555–3565

    PubMed  CAS  Google Scholar 

  • Liu Q, Fischer U, Wang F, Dreyfuss G (1997) The spinal muscular atrophy disease gene product, SMN, and its associasted protein SIP1 are in a complex with spliceosomal snRNP proteins. Cell 90: 1013–1021

    Article  PubMed  CAS  Google Scholar 

  • Lorson CL, Androphy EJ (2000) An exonic enhancer is required for inclusion of an essential exon in the SMA-determining gene SMN. Hum Mol Genet 9: 259–265

    Article  PubMed  CAS  Google Scholar 

  • Lorson CL, Strasswimmer J, Yao JM, Baleja JD, Hahnen E, Wirth B, Le T, Burghes AHM, Androphy EJ (1998) SMN oligomerization defect correlates with spinal muscular atrophy severity. Nat Genet 19: 63–66

    Article  PubMed  CAS  Google Scholar 

  • Lorson CL, Hahnen E, Androphy EJ, Wirth B (1999) A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy. Proc Natl Acad Sci USA 96: 6307–6311

    Article  PubMed  CAS  Google Scholar 

  • Marte BM, Downward J (1997) PKB/Akt: connecting phosphoinositide 3-kinase to cell survival and beyond. Trends Biochem Sci 22: 355–358

    Article  PubMed  CAS  Google Scholar 

  • McAndrew PE, Parsons DW, Simard LR, Rochette C, Ray PN, Mendell JR, Prior TW, Burghes AHM (1997) Identification of proximal spinal muscular atrophy carriers and patients by analysis of SMNT and SMNC gene copy number. Am J Hum Genet 60: 1411–1422

    Article  PubMed  CAS  Google Scholar 

  • Melki J, Abdelhak S, Sheth P, Bachelot MF, Burlet P, Marcadet A, Aicardi J, Barois A, Carriere JP, Fardeau M, Fontan D, Ponsot G, Billette T, Angelini C, Barbosa C, Ferriere G, Lanzi G, Ottolini A, Babron MC, Cohen D, Hanauer A, ClergetDarpoux F, Lathrop M, Munnich A (1990) Gene for chronic proximal spinal muscular atrophies maps to chromosome 5q. Nature 344: 767–768

    Article  PubMed  CAS  Google Scholar 

  • Metzstein MM, Stanfield GM, Horvitz HR (1998) Genetics of programmed cell death in C-elegans: past, present and future. Trends Genet 14: 410–416

    Article  PubMed  CAS  Google Scholar 

  • Monani UR, Lorson CL, Parsons DW, Prior TW, Androphy EJ, Burghes AHM, McPherson JD (2000) A single nucleotide difference that alters splicing patterns distinguishes the SMA gene SMN1 from the copy gene SMN2. Hum Mol Genet 8: 1177–1183

    Article  Google Scholar 

  • Mukasa T, Urase K, Momoi MY, Kimura I, Momoi T (1997) Specific expression of CPP32 in sensory neurons of mouse embryos and activation of CPP32 in the apoptosis induced by a withdrawal of NGF. Biochem Biophys Res Commun 231: 770–774

    Article  PubMed  CAS  Google Scholar 

  • Munsat TL, Davies KE (1992) Meeting report: International SMA Consortium meeting. Neuromusc Disord 2: 423–428

    Article  PubMed  CAS  Google Scholar 

  • Oeda E, Oka Y, Miyazono K, Kawabata M (1998) Interaction of Drosophila inhibitors of apoptosis with thick veins, a type I serine/threonine kinase receptor for decapentaplegic. J Biol Chem 273: 9353–9356

    Article  PubMed  CAS  Google Scholar 

  • Oppenheim RW (1991) Cell death during development of the nervous system. Annu Rev Neurosci 14: 453–501

    Article  PubMed  CAS  Google Scholar 

  • Pearn J (1978) Incidence, prevalence, and gene frequency studies of chronic childhood spinal muscular atrophy. J Med Genet 15: 409–413

    Article  PubMed  CAS  Google Scholar 

  • Pellizzoni L, Kataoka N, Charroux B, Dreyfuss G (1998) A novel function for SMN, the spinal muscular atrophy disease gene product, in pre-mRNA splicing. Cell 95: 615–624

    Article  PubMed  CAS  Google Scholar 

  • Pellizzoni L, Charroux B, Dreyfuss G (1999) SMN mutants of spinal muscular atrophy patients are defective in binding to snRNP proteins. Proc Natl Acad Sci USA 96: 11167–11172

    Article  PubMed  CAS  Google Scholar 

  • Pettmann B, Henderson CE (1998) Neuronal cell death. Neuron 20: 633–647

    Article  PubMed  CAS  Google Scholar 

  • Raff MC, Barres BA, Burne JF, Coles HS, Ishizaki Y, Jacobson MD (1993) Programmed cell death and the control of cell survival: Lessons from the nervous system. Science 262: 695–700

    Article  PubMed  CAS  Google Scholar 

  • Reed JC (1997) Double identity for proteins of the Bc1–2 family. Nature 387: 1–2

    Article  PubMed  CAS  Google Scholar 

  • Rothe M, Pan MG, Henzel WJ, Ayres TM, Goeddel DV (1995) The TNFR2-TRAF signaling complex contains two novel proteins related to baculoviral-inhibitor of apoptosis proteins. Cell 83: 1243–1252

    Article  PubMed  CAS  Google Scholar 

  • Roy N, Mahadevan MS, McLean M, Shutler G, Yaraghi Z, Farahani R, Baird S, BesnerJohnston A, Lefebvre C, Kang X, Salih M, Aubry H, Tamai K, Guan X, Ioannou P, Crawford TO, De Jong PJ, Surh L, Ikeda J-E, Korneluk RG, MacKenzie A (1995) The gene for neuronal apoptosis inhibitory protein is partially deleted in individuals with spinal muscular atrophy. Cell 80: 167–178

    Article  PubMed  CAS  Google Scholar 

  • Roy N, Deveraux QL, Takahashi R, Salvesen GS, Reed JC (1997) The c-IAP-1 and c- IAP-2 proteins are direct inhibitors of specific caspases. EMBO J 16: 6914–6925

    Article  PubMed  CAS  Google Scholar 

  • Salvesen GS, Dixit VM (1997) Caspases: Intracellular signaling by proteolysis. Cell 91: 443–446

    Article  PubMed  CAS  Google Scholar 

  • Schrank B, Götz R, Gunnersen JM, Ure JM, Toyka KV, Smith AG, Sendtner M (1997) Inactivation of the survival motor neuron gene, a candidate gene for human spinal muscular atrophy, leads to massive cell death in early mouse embryos. Proc Natl Acad Sci USA 94: 9920–9925

    Article  PubMed  CAS  Google Scholar 

  • Segal RA, Greenberg ME (1996) Intracellular signaling pathways activated by neurotrophic factors. Annu Rev Neurosci 19: 463–489

    Article  PubMed  CAS  Google Scholar 

  • Seshagiri S, Miller LK (1997) Baculovirus inhibitors of apoptosis (IAPs) block activation of Sf-caspase-1. Proc Natl Acad Sci USA 94: 13606–13611

    Article  PubMed  CAS  Google Scholar 

  • Shaham S, Horvitz HR (1996) An alternatively spliced C-elegans ced-4 RNA encodes a novel cell death inhibitor. Cell 86: 201–208

    Article  PubMed  CAS  Google Scholar 

  • Shu HB, Takeuchi M, Goeddel DV (1996) The tumor necrosis factor receptor 2 signal transducers TRAF2 and c-IAP1 are components of the tumor necrosis factor receptor 1 signaling complex. Proc Natl Acad Sci USA 93: 13973–13978

    Article  PubMed  CAS  Google Scholar 

  • Simons M, Beinroth S, Gleichmann M, Liston P, Korneluk RG, MacKenzie AE, Bähr M, Klockgether T, Robertson GS, Weller M, Schulz JB (1999) Adenovirus-mediated gene transfer of inhibitors of apoptosis protein delays apoptosis in cerebellar granule neurons. J Neurochem 72: 292–301

    Article  PubMed  CAS  Google Scholar 

  • Snider WD (1994) Functions of the neurotrophins during nervous system development: What the knockouts are teaching us. Cell 77: 627–638

    Article  PubMed  Google Scholar 

  • Stefanis L, Park DS, Yan CYI, Farinelli SE, Troy CM, Shelanski ML, Greene LA (1996) Induction of CPP32-like activity in PC12 cells by withdrawal of trophic support-A; Dissociation from apoptosis. J Biol Chem 271: 30663–30671

    Article  PubMed  CAS  Google Scholar 

  • Stehlik C, De Martin R, Binder BR, Lipp J (1998) Cytokine induced expression of porcine inhibitor of apoptosis protein (iap) family member is regulated by NFkappaB. Biochem Biophys Res Commun 243: 827–832

    Article  PubMed  CAS  Google Scholar 

  • Sun CH, Cai ML, Gunasekera AH, Meadows RP, Wang H, Chen J, Zhang HC, Wu W, Xu N, Ng SC, Fesik SW (1999) NMR structure and mutagenesis of the inhibitorof-apoptosis protein XIAP. Nature 401: 818–822

    Article  PubMed  CAS  Google Scholar 

  • Takahashi R, Deveraux Q, Tamm I, Welsh K, Assa-Munt N, Salvesen GS, Reed JC (1998) A single BIR domain of XIAP sufficient for inhibiting caspases. J Biol Chem 273: 7787–7790

    Article  PubMed  CAS  Google Scholar 

  • Talbot K, Ponting CP, Theodosiou AM, Rodrigues NR, Surtees R, Mountford R, Davies K (1997) Missense mutation clustering in the survival motor neuron gene: a role for a conserved tyrosine and glycine rich region of the protein in RNA metabolism? Hum Mol Genet 6: 497–500

    Article  PubMed  CAS  Google Scholar 

  • Tamm I, Wang Y, Sausville E, Scudiero DA, Vigna N, Oltersdorf T, Redd JC (1998) IAPfamily protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs. Cancer Res 58: 15–20

    Google Scholar 

  • Thornberry NA, Lazebnik Y (1998) Caspases: Enemies within. Science 281: 1312–1316

    Article  PubMed  CAS  Google Scholar 

  • Tran J, Rak J, Sheehan C, Saibil SD, LaCasse E, Korneluk RG, Kerbel RS (1999) Marked induction of the IAP family antiapoptotic proteins survivin and XIAP by VEGF in vascular endothelial cells. BBRC 264: 781–788

    PubMed  CAS  Google Scholar 

  • Uren AG, Pakusch M, Hawkins CJ, Puls KL, Vaux DL (1996) Cloning and expression of apoptosis inhibitory protein homologs that function to inhibit apoptosis and/or bind tumor necrosis factor receptor-associated factors. Proc Natl Acad Sci USA 93: 4974–4978

    Article  PubMed  CAS  Google Scholar 

  • Uren AG, Coulson EJ, Vaux DL (1998) Conservation of baculovirus inhibitor of apoptosis repeat proteins (BIRPs) in viruses, nematodes, vertebrates and yeasts. Trends Biochem Sci 23: 159–162

    Article  PubMed  CAS  Google Scholar 

  • Vojtek AB, Der CJ (1998) Increasing complexity of the Ras signaling pathway. J Biol Chem 273: 19925–19928

    Article  PubMed  CAS  Google Scholar 

  • Vucic D, Kaiser WJ, Miller LK (1998) Inhibitor of apoptosis proteins physically interact with and block apoptosis induced by Drosophila proteins HID and GRIM. Mol Cell Biol 18: 3300–3309

    PubMed  CAS  Google Scholar 

  • Wang CY, Mayo MW, Korneluk RG, Goeddel DV, Baldwin AS, Jr (1998) NF-kappaB antiapoptosis: Induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation. Science 281: 1680–1683

    Article  PubMed  CAS  Google Scholar 

  • Wiese S, Digby MR, Gunnersen JM, Götz R, Pei G, Holtmann B, Lowenthal J, Sendtner M (1999) The anti-apoptotic protein ITA is essential for NGF-mediated survival of embryonic chick neurons. Nat Neurosci 2: 978–983

    Article  PubMed  CAS  Google Scholar 

  • Xia Z, Dickens M, Raingeaud J, Davis RJ, Greenberg ME (1995) Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science 270: 1326–1331

    Article  PubMed  CAS  Google Scholar 

  • Yamaguchi K, Nagai S, Ninomiya-Tsuji J, Nishita M, Tamai K, Irie K, Ueno N, Nishida E, Shibuya H, Matsumoto K (1999) XIAP, a cellular member of the inhibitor of apoptosis protein family, links the receptors to TAB1–TAK1 in the BMP signaling pathway. EMBO J 18: TAB1–TAK1

    Article  PubMed  CAS  Google Scholar 

  • Yaraghi Z, Korneluk RG, McKenzie A (1998) Cloning and characterization of the multiple murine homologues of NAIP (Neuronal apoptosis inhibitory protein). Genomics 51: 107–113

    Article  PubMed  CAS  Google Scholar 

  • Yuan J, Shaham S, Ledoux S, Ellis HM, Horvitz HR (1993) The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-lb-converting enzyme. Cell 75: 641–652

    Article  PubMed  CAS  Google Scholar 

  • Zou H, Henzel WJ, Liu XS, Lutschg A, Wang XD (1997) Apaf-1, a human protein homologous to C-elegans CED-4, participates in cytochrome c-dependent activation of caspase-3. Cell 90: 405–413

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Klinische Forschergruppe Neuroregeneration, Department of Neurology, University of Würzburg, Würzburg, Federal Republic of Germany

    R. Götz

Authors
  1. R. Götz
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Psychiatry, University of Würzburg, Federal Republic of Germany

    P. Riederer

  2. Neurodegenerative Disorders Centre, Faculty of Medicine, University Hospital, Vancouver, B.C., Canada

    D. B. Calne

  3. Schering AG Berlin, Berlin, Federal Republic of Germany

    R. Horowski

  4. Department of Neurology, Juntendo University, Tokyo, Japan

    Y. Mizuno

  5. Department of Neurology, Mount Sinai Medical Center, New York, New York, USA

    C. W. Olanow

  6. Department of Neurology, University of Innsbruck, Innsbruck, Austria

    W. Poewe

  7. Department of Pharmacology, Faculty of Medicine, Technion, Haifa, Israel

    M. B. H. Youdim

Rights and permissions

Reprints and permissions

Copyright information

© 2000 Springer-Verlag Wien

About this paper

Cite this paper

Götz, R. (2000). Regulation of neuronal cell death and differentiation by NGF and IAP family members. In: Riederer, P., et al. Advances in Research on Neurodegeneration. Springer, Vienna. https://doi.org/10.1007/978-3-7091-6301-6_16

Download citation

  • DOI: https://doi.org/10.1007/978-3-7091-6301-6_16

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-211-83537-1

  • Online ISBN: 978-3-7091-6301-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation