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Apoptosis in Caspase-inhibited Neurons

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Abstract

Background

There is growing evidence of apoptosis in neurodegenerative disease. However, it is still unclear whether the pathological manifestations observed in slow neurodegenerative diseases are due to neuronal loss or whether they are related to independent degenerative events in the axodendritic network. It also remains elusive whether a single, caspase-based executing system involving caspases is responsible for neuronal loss by apoptosis.

Materials and Methods

Long-term exposure to the microtubule-disassembling agent, colchicine, was used to disrupt the axodendritic network and eventually trigger caspase-3-mediated apoptosis in cultures of cerebellar granule cells. For this model, we investigated the role of Bcl-2 and caspases in neurite degeneration and death of neuronal somata.

Results

Early degeneration of the axodendritic network occurred by a Bcl-2 and caspase-independent mechanism. Conversely, apoptosis of the cell body was delayed by Bcl-2 and initially blocked by caspase inhibition. However, when caspase activity was entirely blocked by zVAD-fmk, colchicine-exposed neurons still underwent delayed cell death characterized by cytochrome c release, chromatin condensation to irregularly shaped clumps, DNA-fragmentation, and exposure of phosphatidylserine. Inhibitors of the proteasome reduced these caspase-independent apoptotic-like features of the neuronal soma.

Conclusion

Our data suggest that Bcl-2-dependent and caspase-mediated death programs account only partially for neurodegenerative changes in injured neurons. Blockage of the caspase execution machinery may only temporarily rescue damaged neurons and classical apoptotic features can still appear in caspase-inhibited neurons.

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References

  1. Kerr JF, Wyllie AH, Currie AR. (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br. J. Cancer 26: 239–257.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Wyllie AH, Kerr JF, Currie AR. (1980) Cell death: the significance of apoptosis. Int. Rev. Cytol. 68: 251–306.

    Article  CAS  PubMed  Google Scholar 

  3. Raff MC. (1992) Social controls on cell survival and cell death. Nature 356: 397–400.

    Article  CAS  PubMed  Google Scholar 

  4. Oppenheim RW, Schwartz LM, Shatz CJ. (1992) Neuronal death, a tradition of dying. J. Neurobiol. 23: 1111–1115.

    Article  CAS  PubMed  Google Scholar 

  5. Leist M, Nicotera P. (1998) Apoptosis, excitotoxicity, and neuropathology. Exp. Cell Res. 239: 183–201.

    Article  CAS  PubMed  Google Scholar 

  6. Nicotera P, Leist M, Fava E, Berliocchi L, Volbracht C. (2000) Energy requirement for caspase activation and neuronal cell death. Brain Pathol. 10: 276–282.

    Article  CAS  PubMed  Google Scholar 

  7. Stefanis L, Burke RE, Greene LA. (1997) Apoptosis in neurodegenerative disorders. Curr. Opin. Neurol. 10: 299–305.

    Article  CAS  PubMed  Google Scholar 

  8. Mucke L, Masliah E, Yu GQ, et al. (2000) High-level neuronal expression of A β 1–42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation. J. Neurosci. 20: 4050–4058.

    Article  CAS  PubMed  Google Scholar 

  9. Murphy KP, Carter RJ, Lione LA, et al. (2000) Abnormal synaptic plasticity and impaired spatial cognition in mice transgenic for exon 1 of the human Huntington’s disease mutation. J. Neurosci. 20: 5115–5123.

    Article  CAS  PubMed  Google Scholar 

  10. Yamamoto A, Lucas JJ, Hen R. (2000) Reversal of neuropathology and motor dysfunction in a conditional model of Huntington’s disease. Cell 101: 57–66.

    Article  CAS  PubMed  Google Scholar 

  11. Braak E, Braak H, Mandelkow EM. (1994) A sequence of cytoskeleton changes related to the formation of neurofibrillary tangles and neuropil threads. Acta Neuropathol. 87:554–567.

    Article  CAS  PubMed  Google Scholar 

  12. Johnson EM, Deckwerth TL. (1993) Molecular mechanisms of developmental neuronal death. Annu. Rev. Neurosci. 16: 31–46.

    Article  CAS  PubMed  Google Scholar 

  13. Bibb JA, Yan Z, Svenningsson P, et al. (2000) Severe deficiencies in dopamine signaling in presymptomatic Huntington’s disease mice. Proc. Natl. Acad. Sci. USA 97: 6809–6814.

    Article  CAS  PubMed  Google Scholar 

  14. Carter RJ, Lione LA, Humby T, et al. (1999) Characterization of progressive motor deficits in mice transgenic for the human Huntington’s disease mutation. J. Neurosci. 19: 3248–3257.

    Article  CAS  PubMed  Google Scholar 

  15. Chapman PF, White GL, Jones MW, et al. (1999) Impaired synaptic plasticity and learning in aged amyloid precursor protein transgenic mice. Nat. Neurosci. 2: 271–276.

    Article  CAS  PubMed  Google Scholar 

  16. Nicholson DW. (1999) Caspase structure, proteolytic substrates, and function during apoptotic cell death. Cell Death Differ. 6: 1028–1042.

    Article  CAS  PubMed  Google Scholar 

  17. Hara H, Friedlander RM, Gagliardini V, et al. (1997) Inhibition of interleukin 1 β converting enzyme family proteases reduces ischemic and excitotoxic neuronal damage. Proc. Natl. Acad. Sci. USA 94: 2007–2012.

    Article  CAS  PubMed  Google Scholar 

  18. Loddick SA, MacKenzie A, Rothwell NJ. (1996) An ICE inhibitor, z-VAD-DCB attenuates ischaemic brain damage in the rat. Neuroreport 7: 1465–1468.

    Article  CAS  PubMed  Google Scholar 

  19. Li M, Ona VO, Guegan C, et al. (2000) Functional role of caspase-1 and caspase-3 in an ALS transgenic mouse model. Science 288: 335–339.

    Article  CAS  PubMed  Google Scholar 

  20. Ona VO, Li M, Vonsattel JP, et al. (1999) Inhibition of caspase-1 slows disease progression in a mouse model of Huntington’s disease. Nature 399: 263–267.

    Article  CAS  PubMed  Google Scholar 

  21. Johnson MD, Xiang H, London S, et al. (1998) Evidence for involvement of Bax and p53, but not caspases, in radiation-induced cell death of cultured postnatal hippocampal neurons. J. Neurosci. Res. 54: 721–733.

    Article  CAS  PubMed  Google Scholar 

  22. Stefanis L, Park DS, Friedman WJ, Greene LA. (1999) Caspase-dependent and -independent death of camptothecintreated embryonic cortical neurons. J. Neurosci. 19: 6235–6247.

    Article  CAS  PubMed  Google Scholar 

  23. Miller TM, Moulder KL, Knudson CM, et al. (1997) Bax deletion further orders the cell death pathway in cerebellar granule cells and suggests a caspase-independent pathway to cell death. J. Cell Biol. 139: 205–217.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Selznick LA, Zheng TS, Flavell RA, Rakic P, Roth KA. (2000) Amyloid β-induced neuronal death is bax-dependent but caspase-independent. J. Neuropathol. Exp. Neurol. 59: 271–279.

    Article  CAS  PubMed  Google Scholar 

  25. Deshmukh M, Vasilakos J, Deckwerth TL, Lampe PA, Shivers BD, Johnson EM. (1996) Genetic and metabolic status of NGF-deprived sympathetic neurons saved by an inhibitor of ICE family proteases. J. Cell Biol. 135: 1341–1354.

    Article  CAS  PubMed  Google Scholar 

  26. Deshmukh M, Kuida K, Johnson EM. (2000) Caspase inhibition extends the commitment to neuronal death beyond cytochrome c release to the point of mitochondrial depolarization. J. Cell Biol. 150: 131–143.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Samali A, Zhivotovsky B, Jones D, Nagata S, Orrenius S. (1999) Apoptosis: cell death defined by caspase activation. Cell Death Differ. 6: 495–496.

    Article  CAS  PubMed  Google Scholar 

  28. Leist M, Single B, Castoldi AF, Kühnle S, Nicotera P. (1997) Intracellular adenosine triphosphate (ATP) concentration: a switch in the decision between apoptosis and necrosis. J. Exp. Med. 185: 1481–1486.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Nicotera P, Leist M, Manzo L. (1999) Neuronal cell death: a demise with different shapes. Trends Pharmacol. Sci. 20: 46–51.

    Article  CAS  PubMed  Google Scholar 

  30. Mattson MP, Keller JN, Begley JG. (1998) Evidence for synaptic apoptosis. Exp. Neurol. 153: 35–48.

    Article  CAS  PubMed  Google Scholar 

  31. Finn JT, Weil M, Archer F, Siman R, Srinivasan A, Raff MC. (2000) Evidence that Wallerian degeneration and localized axon degeneration induced by local neurotrophin deprivation do not involve caspases. J. Neurosci. 20: 1333–1341.

    Article  CAS  PubMed  Google Scholar 

  32. Bonfoco E, Ceccatelli S, Manzo L, Nicotera P. (1995) Colchicine induces apoptosis in cerebellar granule cells. Exp. Cell Res. 218: 189–200.

    Article  CAS  PubMed  Google Scholar 

  33. Volbracht C, Leist M, Nicotera P. (1999) ATP controls neuronal apoptosis triggered by microtubule breakdown or potassium deprivation. Mol. Med. 5: 477–489.

    PubMed  PubMed Central  CAS  Google Scholar 

  34. Martinou JC, Dubois-Dauphin M, Staple JK, et al. (1994) Overexpression of BCL-2 in transgenic mice protects neurons from naturally occurring cell death and experimental ischemia. Neuron 13: 1017–1030.

    Article  CAS  PubMed  Google Scholar 

  35. Leist M, Volbracht C, Fava E, Nicotera P. (1998) 1-methyl-4-phenylpyridinium induces autocrine excitotoxicity, protease activation, and Neuronal apoptosis. Mol. Pharmacol. 54: 789–801.

    Article  CAS  PubMed  Google Scholar 

  36. Single B, Leist M, Nicotera P. (1998) Simultaneous release of adenylate kinase and cytochrome c in cell death. Cell Death Differ. 5: 1001–1003.

    Article  CAS  PubMed  Google Scholar 

  37. Leist M, Volbracht C, Kühnle S, Fava E, Ferrando-May E, Nicotera P. (1997) Caspase-mediated apoptosis in Neuronal excitotoxicity triggered by nitric oxide. Mol. Med. 3: 750–764.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Van de Craen M, Vandenabeele P, Declercq W, et al. (1997) Characterization of seven murine caspase family members. FEBS Lett. 403: 61–69.

    Article  PubMed  Google Scholar 

  39. Kipp M, Schwab BL, Przybylski M, Nicotera P, Fackelmayer FO. (2000) Apoptotic cleavage of scaffold attachment factor A (SAF-A) by caspase-3 occurs at a noncanonical cleavage site. J. Biol. Chem. 275: 5031–5036.

    Article  CAS  PubMed  Google Scholar 

  40. Leist M, Single B, Künstle G, Volbracht C, Hentze H, Nicotera P. (1997) Apoptosis in the absence of poly-(ADP-ribose) polymerase. Biochem. Biophys. Res. Commun. 233: 518–522.

    Article  CAS  PubMed  Google Scholar 

  41. Talanian RV, Quinlan C, Trautz S, et al. (1997) Substrate specificities of caspase family proteases. J. Biol. Chem. 272: 9677–9682.

    Article  CAS  PubMed  Google Scholar 

  42. Thornberry NA. (1994) Interleukin-1 β converting enzyme. Methods Enzymol. 244: 615–631.

    Article  CAS  PubMed  Google Scholar 

  43. Garcia-Calvo M, Peterson EP, Rasper DM, et al. (1999) Purification and catalytic properties of human caspase family members. Cell Death Differ. 6: 362–369.

    Article  CAS  PubMed  Google Scholar 

  44. Haldar S, Basu A, Croce CM. (1997) Bcl2 is the guardian of microtubule integrity. Cancer Res. 57: 229–233.

    PubMed  CAS  Google Scholar 

  45. Green DR, Reed JC. (1998) Mitochondria and apoptosis. Science 281: 1309–1312.

    Article  CAS  PubMed  Google Scholar 

  46. Haraguchi M, Torii S, Matsuzawa S, et al. (2000) Apoptotic protease activating factor 1 (Apaf-1)-independent cell death suppression by bcl-2. J. Exp. Med. 191: 1709–1720.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Garcia-Calvo M, Peterson EP, Leiting B, Ruel R, Nicholson DW, Thornberry NA. (1998) Inhibition of human caspases by peptide-based and macromolecular inhibitors. J. Biol. Chem. 273: 32608–32613.

    Article  CAS  PubMed  Google Scholar 

  48. Troy CM, Rabacchi SA, Friedman WJ, Frappier TF, Brown K, Shelanski ML. (2000) Caspase-2 mediates Neuronal cell death induced by β-amyloid. J. Neurosci. 20: 1386–1392.

    Article  CAS  PubMed  Google Scholar 

  49. Putcha GV, Deshmukh M, Johnson EM. (2000) Inhibition of apoptotic signaling cascades causes loss of trophic factor dependence during Neuronal maturation. J. Cell. Biol. 149: 1011–1018.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Gagliardini V, Fernandez PA, Lee RK, et al. (1994) Prevention of vertebrate Neuronal death by the crmA gene. Science 263: 826–828.

    Article  CAS  PubMed  Google Scholar 

  51. Enari M, Hug H, Nagata S. (1995) Involvement of an ICE-like protease in Fas-mediated apoptosis. Nature 375: 78–81.

    Article  CAS  PubMed  Google Scholar 

  52. Milligan CE, Prevette D, Yaginuma H, et al. (1995) Peptide inhibitors of the ICE protease family arrest programmed cell death of motoneurons in vivo and in vitro. Neuron 15: 385–393.

    Article  CAS  PubMed  Google Scholar 

  53. Stefanis L, Park DS, Yan CY, et al. (1996) Induction of CPP32-like activity in PC12 cells by withdrawal of trophic support. Dissociation from apoptosis. J. Biol. Chem. 271: 30663–30671.

    Article  CAS  PubMed  Google Scholar 

  54. Troy CM, Stefanis L, Prochiantz A, Greene LA, Shelanski ML. (1996) The contrasting roles of ICE family proteases and interleukin-1β in apoptosis induced by trophic factor withdrawal and by copper/zinc superoxide dismutase down-regulation. Proc. Natl. Acad. Sci. USA 93: 5635–5640.

    Article  CAS  PubMed  Google Scholar 

  55. de Bilbao F, Dubois-Dauphin M. (1996) Acute application of an interleukin-1 β-converting enzyme-specific inhibitor delays axotomy-induced motoneurone death. Neuroreport 7: 3051–3054.

    Article  PubMed  Google Scholar 

  56. Yakovlev AG, Knoblach SM, Fan L, Fox GB, Goodnight R, Faden AI. (1997) Activation of CPP32-like caspases contributes to Neuronal apoptosis and neurological dysfunction after traumatic brain injury. J. Neurosci. 17: 7415–7424.

    Article  CAS  PubMed  Google Scholar 

  57. Schierle GS, Hansson O, Leist M, Nicotera P, Widner H, Brundin P. (1999) Caspase inhibition reduces apoptosis and increases survival of nigral transplants. Nat. Med. 5: 97–100.

    Article  CAS  PubMed  Google Scholar 

  58. Doerfler P, Forbush KA, Perlmutter RM. (2000) Caspase enzyme activity is not essential for apoptosis during thymocyte development. J. Immunol. 164: 4071–4079.

    Article  CAS  PubMed  Google Scholar 

  59. Chautan M, Chazal G, Cecconi F, Gruss P, Golstein P. (1999) Interdigital cell death can occur through a necrotic and caspase-independent pathway. Curr. Biol. 9: 967–970.

    Article  CAS  PubMed  Google Scholar 

  60. Amarante-Mendes GP, Finucane DM, Martin SJ, Cotter TG, Salvesen GS, Green DR. (1998) Anti-apoptotic oncogenes prevent caspase-dependent and independent commitment for cell death. Cell Death Differ. 5: 298–306.

    Article  CAS  PubMed  Google Scholar 

  61. Hirsch T, Marchetti P, Susin SA, et al. (1997) The apoptosisnecrosis paradox. Apoptogenic proteases activated after mitochondrial permeability transition determine the mode of cell death. Oncogene 15: 1573–1581.

    Article  CAS  PubMed  Google Scholar 

  62. Sarin A, Williams MS, Alexander-Miller MA, Berzofsky JA, Zacharchuk CM, Henkart PA. (1997) Target cell lysis by CTL granule exocytosis is independent of ICE/Ced-3 family proteases. Immunity 6: 209–215.

    Article  CAS  PubMed  Google Scholar 

  63. Trapani JA, Jans DA, Jans PJ, Smyth MJ, Browne KA, Sutton VR. (1998) Efficient nuclear targeting of granzyme B and the nuclear consequences of apoptosis induced by granzyme B and perforin are caspase-dependent, but cell death is caspase-independent. J. Biol. Chem. 273: 27934–27938.

    Article  CAS  PubMed  Google Scholar 

  64. Chi S, Kitanaka C, Noguchi K, et al. (1999) Oncogenic Ras triggers cell suicide through the activation of a caspase-independent cell death program in human cancer cells. Oncogene 18: 2281–2290.

    Article  CAS  PubMed  Google Scholar 

  65. Kawahara A, Ohsawa Y, Matsumura H, Uchiyama Y, Nagata S. (1998) Caspase-independent cell killing by Fas-associated protein with death domain. J. Cell. Biol. 143: 1353–1360.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Nylansted J, Rohde M, Brand K, Bastholm L, Elling F, Jäättelä M. (2000) Inhibition of Hsp70 synthesis activates a novel caspase-independent and Bcl-2 resistant death pathway in breast cancer cells. Proc. Natl. Acad. Sci. USA 97: 7871–7876.

    Article  Google Scholar 

  67. McCarthy NJ, Whyte MK, Gilbert CS, Evan GI. (1997) Inhibition of Ced-3/ICE-related proteases does not prevent cell death induced by oncogenes, DNA damage, or the Bcl-2 homologue Bak. J. Cell. Biol. 136: 215–227.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Monney L, Otter I, Olivier R, et al. (1998) Defects in the ubiquitin pathway induce caspase-independent apoptosis blocked by Bcl-2. J. Biol. Chem. 273: 6121–6131.

    Article  CAS  PubMed  Google Scholar 

  69. Brunet CL, Gunby RH, Benson RS, Hickman JA, Watson AJ, Brady G. (1998) Commitment to cell death measured by loss of clonogenicity is separable from the appearance of apoptotic markers. Cell Death Differ. 5: 107–115.

    Article  CAS  PubMed  Google Scholar 

  70. Déas O, Dumont C, MacFarlane M, et al. (1998) Caspase-in-dependent cell death induced by anti-CD2 or staurosporine in activated human peripheral T lymphocytes. J. Immunol. 161: 3375–3383.

    PubMed  Google Scholar 

  71. Xiang J, Chao DT, Korsmeyer SJ. (1996) BAX-induced cell death may not require interleukin 1 β-converting enzymelike proteases. Proc. Natl. Acad. Sci. USA 93: 14559–14563.

    Article  CAS  PubMed  Google Scholar 

  72. Enari M, Sakahira H, Yokoyama H, Okawa K, Iwamatsu A, Nagata S. (1998) A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD. Nature 391: 43–50.

    Article  CAS  PubMed  Google Scholar 

  73. Martin SJ, Finucane DM, Amarante-Mendes GP, O’Brien GA, Green DR. (1996) Phosphatidylserine externalization during CD95-induced apoptosis of cells and cytoplasts requires ICE/CED-3 protease activity. J. Biol. Chem. 271: 28753–28756.

    Article  CAS  PubMed  Google Scholar 

  74. Hirt UA, Gantner F, Leist M. (2000) Phagocytosis of non-apoptotic cells dying by caspase- independent mechanisms. — J. Immunol. 164: 6520–6529.

    Article  CAS  PubMed  Google Scholar 

  75. Susin SA, Lorenzo HK, Zamzami N, et al. (1999) Mitochondrial release of caspase-2 and -9 during the apoptotic process. J. Exp. Med. 189: 381–394.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Liu X, Kim CN, Yang J, Jemmerson R, Wang X. (1996) Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell 86: 147–157.

    Article  CAS  PubMed  Google Scholar 

  77. Susin SA, Zamzami N, Castedo M, et al. (1996) Bcl-2 inhibits the mitochondrial release of an apoptogenic protease. J. Exp. Med. 184: 1331–1341.

    Article  CAS  PubMed  Google Scholar 

  78. Bernardi P, Colonna R, Costantini P, et al. (1998) The mitochondrial permeability transition. Biofactors 8: 273–281.

    Article  CAS  PubMed  Google Scholar 

  79. Tsujimoto Y, Shimizu S, Eguchi Y, Kamiike W, Matsuda H. (1997) Bcl-2 and Bcl-xL block apoptosis as well as necrosis: possible involvement of common mediators in apoptotic and necrotic signal transduction pathways. Leukemia 11: 380–382.

    PubMed  Google Scholar 

  80. Kane DJ, Ord T, Anton R, Bredesen DE. (1995) Expression of bcl-2 inhibits necrotic neural Cell death. J. Neurosci. Res. 40: 269–275.

    Article  CAS  PubMed  Google Scholar 

  81. Kroemer G, Reed JC. (2000) Mitochondrial control of Cell death. Nat. Med. 6: 513–519.

    Article  CAS  PubMed  Google Scholar 

  82. Susin SA, Lorenzo HK, Zamzami N, et al. (1999) Molecular characterization of mitochondrial apoptosis-inducing factor. Nature 397: 441–446.

    Article  CAS  PubMed  Google Scholar 

  83. Squier MK, Miller AC, Malkinson AM, Cohen JJ. (1994) Calpain activation in apoptosis. J. Cell. Physiol. 159: 229–237.

    Article  CAS  PubMed  Google Scholar 

  84. Deiss LP, Galinka H, Berissi H, Cohen O, Kimchi A. (1996) Cathepsin D protease mediates programmed Cell death induced by interferon-γ, Fas/APO-1 and TNF-γ. Embo J. 15: 3861–3870.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  85. Grimm LM, Goldberg AL, Poirier GG, Schwartz LM, Osborne BA. (1996) Proteasomes play an essential role in thymocyte apoptosis. Embo J. 15: 3835–3844.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  86. Wright SC, Schellenberger U, Wang H, Kinder DH, Talhouk JW, Larrick JW. (1997) Activation of CPP32-like proteases is not sufficient to trigger apoptosis: inhibition of apoptosis by agents that suppress activation of AP24, but not CPP32-like activity. J. Exp. Med. 186: 1107–1117.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Canu N, Barbato C, Ciotti MT, Serafino A, Dus L, Calissano P. (2000) Proteasome involvement and accumulation of ubiquitinated proteins in cerebellar granule neurons undergoing apoptosis. J. Neurosci. 20: 589–599.

    Article  CAS  PubMed  Google Scholar 

  88. Sadoul R, Fernandez PA, Quiquerez AL, et al. (1996) Involvement of the proteasome in the programmed Cell death of NGF-deprived sympathetic neurons. Embo J. 15: 3845–3852.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Acknowledgement

The excellent technical assistance of M. Häberlin, N. Fehrenbacher, H. Naumann, and T. Schmitz is gratefully acknowledged. We are grateful to Dr. J.-C. Martinou (Geneva, Switzerland) for providing Bcl-2 transgenic mice, to Dr. P. Vandenabeele (Gent, Belgium) for providing recombinant caspase-2, and to Dr. F.O. Fackelmayer (Konstanz, Germany) for providing recombinant caspase-3. The Land BadenWürttemberg, the DFG grants We686/18-1, Ni519/1-1, and Ni519/2-1, and the EEC grants BMH4CT97-2410 and 12029-97-06 F1ED ISP D supported this study.

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  1. Department of Biology, University of Konstanz, Box X911, 78457, Konstanz, Germany

    Christiane Volbracht, Marcel Leist &  Pierluigi Nicotera (Chair of Molecular Toxicology)

  2. Laboratory for Electron Microscopy, Department of Pathology, University Hospital Zurich, Zurich, Switzerland

    Stefan A. Kolb

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  1. Christiane Volbracht
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Correspondence to Pierluigi Nicotera.

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Volbracht, C., Leist, M., Kolb, S.A. et al. Apoptosis in Caspase-inhibited Neurons. Mol Med 7, 36–48 (2001). https://doi.org/10.1007/BF03401837

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