Skip to main content
SpringerLink
Log in

Apoptosis Versus Necrosis: The Shape of Neuronal Cell Death

  • Chapter
Apoptosis: Mechanisms and Role in Disease

Part of the book series: Results and Problems in Cell Differentiation ((RESULTS,volume 24))

Abstract

Besides modelling the nervous system during development, excessive apoptotic cell death can take place in neurodegenerative diseases. Key molecules, which participate in the regulation and execution of apoptosis in non-neuronal cells (i.e., caspases, calpains, Bcl-2 related proteins and p53), seem to play important roles also in the death of cells of the nervous system. In addition, neuron specific death mechanisms have been unravelled, which are based on specific neuronal characteristics such as excitability and specific channels or enzymes. Particularly important for stroke in humans is excitotoxicity, which can result in either neuronal apoptosis or necrosis. Here, we will briefly review the evidence for the involvement of apoptosis in the pathology of the nervous system.

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 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight 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

  • Adle-Biassette H, Levy Y, Colombel M, Poron F, Natchev S, Keohane C, Gray F (1995) Neuronal apoptosis in HIV infection in adults. Neuropathol Appl Neurobiol 21:218–227

    CAS  PubMed  Google Scholar 

  • Aguzzi A (1996) Between cows and monkeys. Nature 381:734–735

    CAS  PubMed  Google Scholar 

  • Albin RL, Greenamyre JT (1992) Alternative excitotoxic hypotheses. Neurology 42:733–738

    CAS  PubMed  Google Scholar 

  • Allsopp TE, Wyatt S, Paterson HF, Davies AM (1993) The proto-oncogene bcl-2 can selectively rescue neurotrophic factor-dependent neurons from apoptosis. Cell 73:295–307

    CAS  PubMed  Google Scholar 

  • Anglade P, Vyas S, Javoy-Agid F, Herrero MT, Michel PP, Marquez J, Mouatt-Prigent A, Ruberg M, Hirsch EC, Agid Y (1997) Apoptosis and autophagy in nigral neurons of patients with Parkinson’s disease. Histol Histopathol 12:25–31

    CAS  PubMed  Google Scholar 

  • Ankarcrona M, Dypbukt JM, Bonfoco E, Zhivotovsky B, Orrenius S, Lipton SA, Nicotera P (1995) Glutamate-induced neuronal death: a succession of necrosis or apoptosis depending on mitochondrial function. Neuron 15:961–973

    CAS  PubMed  Google Scholar 

  • Arenas E, Persson H (1994) Neurotrophin-3 prevents the death of adult central noradrenergic neurons in vivo. Nature 367:368–371

    CAS  PubMed  Google Scholar 

  • Armstrong RC, Aja TJ, Hoang KD, Gaur S, Bai X, Alnemri ES, Litwack G, Karanewsky DS, Fritz LC, Tomaselli KJ (1997) Activation of the Ced3/ICE-related protease CPP32 in cerebellar granule neurons undergoing apoptosis but not necrosis. J Neurosci 17:553–562

    CAS  PubMed  Google Scholar 

  • Bagetta G, Nisticö G, Bowery NG (1990) Prevention by the NMDA receptor antagonist, of neuronal loss produced by tetanus toxin in the rat hippocampus. Br J Pharmacol 101:776–780

    CAS  PubMed  Google Scholar 

  • Bagetta G, Corasaniti T, Berliocchi L, Navarra M, Finazzi-Agró A, Nisticó G (1995) HIV-1 gp120 produces DNA fragmentation in the cerebral cortex of rat. Biochem Biophys Res Commun 211:130–136

    CAS  PubMed  Google Scholar 

  • Bagetta G, Corasaniti MT, Malorni W, Rainaldi G, Berliocchi L, Finazzi-Agrò A, Nisticò G (1996) The HIV-1 gp120 causes ultrastructural changes typical to apoptosis in the rat cerebral cortex. NeuroReport 7:1722–1724

    CAS  PubMed  Google Scholar 

  • Barres BA, Hart IK, Coles HSR, Burne JF, Voyvodic JT, Richardson WD, Raff MC (1992) Cell death and control of cell survival in the oligodendrocyte lineage. Cell 70:31–46

    CAS  PubMed  Google Scholar 

  • Barres BA, Schmid R, Sendtner M, Raff MC (1993) Multiple extracellular signals are required for long-term oligodendrocyte survival. Development 118:283–295

    CAS  PubMed  Google Scholar 

  • Barrett GL, Bartlett PF (1994) The p75 nerve growth factor receptor mediates survival or death depending on the stage of sensory neuron development. Proc Natl Acad Sci USA 91:6501–6505

    CAS  PubMed  Google Scholar 

  • Beal MF (1996) Mitochondria, free radicals, and neurodegeneration. Curr Opin Neurobiol 6:661–666

    CAS  PubMed  Google Scholar 

  • Beal MF, Hyman BT, Koroshetz W (1993) Do defects in mitochondrial energy metabolism underlie the pathology of neurodegenerative diseases? Trends Neurosci 16:125–131

    CAS  PubMed  Google Scholar 

  • Beckman JS, Koppenol WH (1996) Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and the ugly. Am J Physiol 271:C1424–C1437

    Google Scholar 

  • Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA (1990) Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci USA 87:1620–1624

    CAS  PubMed  Google Scholar 

  • Beckmann JS, Ye ZY, Anderson PG, Chen J, Accavitti MA, Tarpey MM, White CR (1994) Extensive nitration of protein tyrosines in human atherosclerosis detected by immunohistochemistry. Biol Chem Hoppe-Seyler 375:81–88

    CAS  PubMed  Google Scholar 

  • Beckman JS, Chen J, Ischiropoulos H, Crow JP (1995) Oxidative chemistry of peroxynitrite. Meth Enyzmol 233:229–240

    Google Scholar 

  • Beilharz EJ, Williams CE, Dragunow M, Sirimanne ES, Gluckman PD (1995) Mechanisms of delayed cell death following hypoxic-ischemic injury in the immature rat: evidence for apoptosis during selective neuronal loss. Mol Brain Res 29:1–14

    CAS  PubMed  Google Scholar 

  • Berkelaar M, Clarke DB, Wang YC, Bray GM, Aguayo AJ (1994) Axotomy results in delayed death and apoptosis of retinal ganglion cells in adult rats. J Neurosci 14:4368–4374

    CAS  PubMed  Google Scholar 

  • Blaschke AJ, Staley K, Chun J (1996) Widespread programmed cell death in proliferative and postmitotic regions of the fetal cerebral cortex. Development 122:1165–1174

    CAS  PubMed  Google Scholar 

  • Bolanos JP, Heales SJR, Land JM, Clark JB (1995) Effect of peroxynitrite on the mitochondrial respiratory chain: differential susceptibility of neurones and astrocytes in primary culture. J Neurochem 64:1965–1972

    CAS  PubMed  Google Scholar 

  • Bonetti B, Raine CS (1997) Multiple sclerosis: oligodendrocytes display cell death-related molecules in situ but do not undergo apoptosis. Ann Neurol 42:74–84

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Bonfoco E, Krainc D, Ankarcrona M, Nicotera P, Lipton SA (1995b) Apoptosis and necrosis: two distinct events induced respectively by mild and intense insults with NMDA or nitric oxide/superoxide in cortical cell cultures. Proc Natl Acad Sci USA 92:72162–72166

    Google Scholar 

  • Bonfoco E, Leist M, Zhivotovsky B, Orrenius S, Lipton SA, Nicotera P (1996a) Cytoskeletal breakdown and apoptosis elicited by NO-donors in cerebellar granule cells require NMDA-receptor activation. J Neurochem 67:2484–2493

    CAS  PubMed  Google Scholar 

  • Bonfoco E, Zhivotovsky B, Rossi AD, Aguillar-Santelises M, Orrenius S, Lipton SA, Nicotera P (1996b) Bcl-2 delays apoptosis and PARP cleavage induced by NO-donors in GT1–7 cells. NeuroReport 8:273–276

    CAS  PubMed  Google Scholar 

  • Brouillet E, Beal MF (1993) NMDA antagonists partially protect against MPTP induced neurotoxicity in mice. Neuroreport 4:387–390

    CAS  PubMed  Google Scholar 

  • Brugg B, Michel PP, Agid Y, Ruberg M (1996) Ceramide induces apoptosis in cultured mesencephalic neurons. J Neurochem 66:733–739

    CAS  PubMed  Google Scholar 

  • Budd SL, Nicholls DG (1996) Mitochondria, calcium regulation, and acute glutamate excitotoxicity in cultured cerebellar granule cells. J Neurochem 67:2282–2291

    CAS  PubMed  Google Scholar 

  • Casaccia-Bonnefil P, Carter BD, Dobrowsky RD, Chao MV (1996) Death of oligodendrocytes mediated by the interaction of nerve growth factor with its receptor p75. Nature 383:716–720

    CAS  PubMed  Google Scholar 

  • Chang G-Q, Hao Y, Wong F (1993) Apoptosis: final common pathway of photoreceptor death in rd, rds, and rhodopsin mutant mice. Neuron 11:595–605

    CAS  PubMed  Google Scholar 

  • Charriaut-Marlangue C, Margaill I, Plotkine M, Ben-Ari Y (1995) Early endonuclease activation following reversible focal ischemia in the rat brain. J Cereb Blood Flow Metab 15:385–388

    CAS  PubMed  Google Scholar 

  • Charriaut-Marlangue C, Aggoun-Zouaoui D, Represa A, Ben-Ari Y (1996a) Apoptotic features of selective neuronal death in ischemia, epilepsy and gp120 toxicity. Trends Neurosci 19:109–114

    CAS  PubMed  Google Scholar 

  • Charriaut-Marlangue C, Margaill I, Borrega F, Plotkine M, Ben-Ari Y (1996b) NG-nitro-L-arginine methyl ester reduces necrotic but not apoptotic cell death induced by reversible focal ischemia in rat. Eur J Pharmacol 310:137–140

    CAS  PubMed  Google Scholar 

  • Chen J, Zhu RL, Nakayama M, Kawaguchi K, Jin K, Stetler RA, Simon RP, Graham SH (1996) Expression of the apoptosis-effector gene, Bax, is up-regulated in vulnerable hippocampal CA1 neurons following global ischemia. J Neurochem 67:64–71

    CAS  PubMed  Google Scholar 

  • Choi DW (1988) Glutamate neurotoxicity and diseases of the nervous system. Neuron 1:623–634

    CAS  PubMed  Google Scholar 

  • Choi DW (1995) Calcium: still center-stage in hypoxic-ischemic neuronal death. Trends Neurosci 18:58–60

    CAS  PubMed  Google Scholar 

  • Choi DW, Rothman SM (1990) The role of glutamate neurotoxicity in hypoxic-ischemic neuronal death. Annu Rev Neurosci 13:171–182

    CAS  PubMed  Google Scholar 

  • Crow JP, Beckman JS (1995) Reactions between nitric oxide, superoxide, and peroxynitrite: footprints of peroxynitrite in vivo. Adv Pharmacol 34:17–43

    CAS  PubMed  Google Scholar 

  • Dawson VL, Dawson TM, Bartley DA, Uhl GR, Snyder SH (1993) Mechanisms of nitric oxide-mediated neurotoxicity in primary brain cultures. J Neurosci 13:2651–2661

    CAS  PubMed  Google Scholar 

  • Deckwerth TL, Johnson EM Jr (1993) Neurotrophic factor deprivation-induced death. Ann NY Acad Sci 679:121–131

    CAS  PubMed  Google Scholar 

  • Deckwerth TL, Elliott JL, Knudson CM, Johnson EM Jr, Snider WD, Korsmeyer SJ (1996) BAX is required for neuronal death after trophic factor deprivation and during development. Neuron 17:401–411

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Dessi F, Pollard H, Moreau J, Ben-Ari Y, Charriaut-Marlangue C (1995) Cytosine arabinoside induces apoptosis in cerebellar neurons in culture. J Neurochem 64:1980–1987

    CAS  PubMed  Google Scholar 

  • Dimmeler S, Haendeler J, Nehls M, Zeiher AM (1997) Suppression of apoptosis by nitric oxide via inhibition of interleukin-lbeta-converting enzyme (ICE)-like and cysteine protease protein (CPP)-32-like proteases. J Exp Med 185:601–607

    CAS  PubMed  Google Scholar 

  • Dipasquale B, Marini AM, Youle RJ (1991) Apoptosis and DNA degradation induced by 1-methyl-4-phenylpyridinium in neurons. Biochem Biophys Res Commun 181:1442–1448

    CAS  PubMed  Google Scholar 

  • D’Mello S, Galli C, Ciotti T, Calissano P (1989) Induction of apoptosis in cerebellar granule neurons by low potassium: inhibition of death by insulin-like growth factor I and cAMP. Proc Natl Acad Sci USA 90:10989–10993

    Google Scholar 

  • Dowling P, Shang G, Raval S, Menonna J, Cook S, Husar W (1996) Involvement of the CD95 (APO-1/Fas) receptor/ligand system in multiple sclerosis brain. J Exp Med 184:1513–1518

    CAS  PubMed  Google Scholar 

  • Dowling P, Husar W, Menonna J, Donnenfeld H, Cook S, Sidhu M (1997) Cell death and birth in multiple sclerosis brain. J Neurol Sci 149:1–11

    CAS  PubMed  Google Scholar 

  • D’Souza SD, Bonetti B, Balasingam V, Cashman NR, Barker PA, Troutt AB, Raine CS, Antel JP (1996) Multiple sclerosis: Fas signaling in oligodendrocyte cell death. J Exp Med 184:2361–2370

    PubMed  Google Scholar 

  • Dragunow M, Faull RLM, Lawlor P, Beilharz EJ, Singleton K, Walker EB, Mee E (1995) In situ evidence for DNA fragmentation in Huntington’s disease striatum and Alzheimer’s disease temporal lobes. NeuroReport 6:1053–1057

    CAS  PubMed  Google Scholar 

  • Drejer J, Beneviste H, Diemer NH, Schousboe A (1985) Cellular origin of ischemia-induced glutamate release from brain tissue in vivo and in vitro. J Neurochem 45:145–151

    CAS  PubMed  Google Scholar 

  • Du Y, Bales KR, Dodel RC, Hamilton-Byrd E, Horn JW, Czilli DL, Simmons LK, Ni B, Paul SM (1997) Activation of a caspase 3-related cysteine protease is required for glutamate-mediated apoptosis of cultured cerebellar granule neurons. Proc Natl Acad Sci USA 94:11657–11662

    CAS  PubMed  Google Scholar 

  • Dudek H, Datta SR, Franke TF, Birnbaum MJ, Yao R, Cooper GM, Segal RA, Kaplan DR, Greenberg ME (1997) Regulation of neuronal survival by the serine-threonine protein kinase Akt. Science 275:661–664

    CAS  PubMed  Google Scholar 

  • Dypbukt JM, Ankarcrona M, Burkitt M, Sjöholm A, Ström K, Orrenius S, Nicotera P (1994) Different prooxidant levels stimulate growth, trigger apoptosis, or produce necrosis of insulin-secreting RINm5F cells. J Biol Chem 269:30533–30560

    Google Scholar 

  • Edwards SN, Buckmaster AE, Tolkovsky AM (1991) The death programme in cultured sympathetic neurones can be suppressed at the posttranslational level by nerve growth factor, cyclic AMP, and depolarization. J Neurochem 57:2140–2143

    CAS  PubMed  Google Scholar 

  • Eitan S, Schwartz M (1993) A transglutaminase that converts interleukin-2 into a factor cytotoxic to oligodendrocytes. Science 261:106–108

    CAS  PubMed  Google Scholar 

  • Eitan S, Solomon A, Lavie V, Yoles E, Hirschberg DL, Belkin M, Schwartz M (1994) Recovery of visual response of injured adult rat optic nerves treated with transglutaminase. Science 264:1764–1768

    CAS  PubMed  Google Scholar 

  • Eizenberg O, Faber-Elman A, Gottlieb E, Oren M, Rotter V, Schwartz M (1995) Direct involvement of p53 in programmed cell death of oligodendrocytes. EMBO J 14:1136–1144

    CAS  PubMed  Google Scholar 

  • Eizenberg O, Faber-Elman A, Gottlieb E, Oren M, Rotter V, Schwartz M (1996) p53 plays a regulatory role in differentiation and apoptosis of central nervous system-associated cells. Mol Cell Biol 16:5178–5185

    CAS  PubMed  Google Scholar 

  • Ekström PAR (1995) Neurons and glial cells of the mouse sciatic nerve undergo apoptosis after injury in vivo and in vitro. NeuroReport 6:1029–1032

    PubMed  Google Scholar 

  • Eliasson MJL, Sampei K, Mandir AS, Hurn PD, Traystman RJ, Bao J, Pieper A, Wang Z-Q, Dawson TM, Snyder SH, Dawson VL (1997) Poly(ADP-ribose) polymerase gene disruption renders mice resistant to cerebral ischemia. Nat Med 3:1089–1095

    CAS  PubMed  Google Scholar 

  • Ellerby HM, Martin SJ, Ellerby LM, Naiem SS, Rabizadeh S, Salvesen GS, Casiano C, Cashman NR, Green DR, Bredesen DE (1997) Establishment of a cell-free system of neuronal apoptosis: comparison of premitochondrial, mitochondrial, and postmitochondrial phases. J Neurosci 17:6165–6178

    CAS  PubMed  Google Scholar 

  • Ellis HM, Horvitz HR (1986) Genetic control of programmed cell death in the nematode C. elegans. Cell 44:817–829

    CAS  PubMed  Google Scholar 

  • Endres M, Wang ZQ, Namura S, Waeber C, Moskowitz MA (1997) Ischemic brain injury is mediated by the activation of poly(ADP-ribose)polymerase. J Cereb Blood Flow Metab 17:1143–1153

    CAS  PubMed  Google Scholar 

  • Estévez AG, Radi R, Barbeito L, Shin JT, Thompson JA, Beckman JS (1995) Peroxynitrite-induced cytotoxicity in PC12 cells: evidence for an apoptotic mechanism differentially modulated by neurotrophic factors. J Neurochem 65:1543–1550

    PubMed  Google Scholar 

  • Fadok VA, Voelker DR, Campbell PA, Cohen JJ, Bratton DL, Henson PM (1992) Particle digestibility is required for induction of the phosphatidylserine recognition mechanism used by murine macrophages to phagocytose apoptotic cells. J Immunol 148:2207–2216

    CAS  PubMed  Google Scholar 

  • Ferrante RJ, Brouillet E, Palfi S, Kowall NW, Hantraye P, Beal MF (1997) Mitochondrial dys-function as a model for Huntington’s disease using the electron transport chain inhibitor 3-nitropropionic acid. In: Beal MF, Howell N, Bodis-Wollner I (eds) Mitochondria and free radicals in neurodegenerative diseases. Wiley-Liss, New York, pp 229–244

    Google Scholar 

  • Ferrari G, Anderson BL, Stephens RM, Kaplan DR, Greene LA (1995) Prevention of apoptotic neuronal death by GM1 ganglioside involvement of Trk neurotrophin receptors. J Biol Chem 270:3074–3080

    CAS  PubMed  Google Scholar 

  • Forloni G, Angeretti N, Chiesa R, Monzani E, Salmona M, Bugiani O, Tagliavini F (1993a) Neurotoxicity of a prion protein fragment. Nature 362:543–546

    CAS  PubMed  Google Scholar 

  • Forloni G, Chiesa R, Smiroldo S, Verga L, Salmona M, Tagliavini F, Angeretti N (1993b) Apoptosis mediated neurotoxicity induced by chronic application of beta amyloid fragment 25–35. NeuroReport 4:523–526

    CAS  PubMed  Google Scholar 

  • Frade JM, Rodríguez-Tébar A, Barde Y-A (1996) Induction of cell death by endogenous nerve growth factor through its p75 receptor. Nature 383:166–168

    CAS  PubMed  Google Scholar 

  • Franklin JL, Sanz-Rodriguez C, Juhasz A, Deckwerth TL, Johnson EM (1995) Chronic depolarization prevents programmed death of sympathetic neurons in vitro but does not support growth: requirement for Ca2+ influx but not Trk activation. J Neurosci 15:643–664

    CAS  PubMed  Google Scholar 

  • Freeman RS, Estus S, Johnson EM (1994) Analysis of cell-cycle-related gene expression in postmitotic neurons: selective induction of cyclin D1 during programmed cell death. Neuron 12:343–355

    CAS  PubMed  Google Scholar 

  • French LE, Hahne M, Viard I, Radlgruber G, Zanone R, Becker K, Müller C, Tschopp J (1996) Fas and Fas ligand in embryos and adult mice: ligand expression in several immune-privileged tissues and coexpression in adult tissues characterized by apoptotic cell turnover. J Cell Biol 133:335–343

    CAS  PubMed  Google Scholar 

  • Friedlander RM, Gagliardini V, Rotello RJ, Yuan J (1996) Functional role of interleukin-1β (IL- 1β) in IL-1β converting enzyme-mediated apoptosis. J Exp Med 184:717–724

    CAS  PubMed  Google Scholar 

  • Galpern WR, Matthews RT, Beal FM, Isacson O (1996) NGF attenuates 3-nitrotyrosine formation in a 3-NP model of Huntington’s disease. NeuroReport 7:2639–2642

    CAS  PubMed  Google Scholar 

  • Garcia-Venezuela E, Shareef S, Walsh J, Sharma SC (1995) Programmed cell death of retinal ganglion cells during experimental glaucoma. Exp Eye Res 61:33–44

    Google Scholar 

  • Garthwaite J, Boulton CL (1995) Nitric oxide signaling in the central nervous system. Annu Rev Physiol 57:683–706

    CAS  PubMed  Google Scholar 

  • Gelbard HA, James HJ, Sharer LR, Perry SW, Saito Y, Kazee AM, Blumberg BM, Epstein LG (1995) Apoptotic neurons in brains from paediatric patients with HIV-1 encephalitis and progressive encephalopathy. Neuropathol Appl Neurobiol 21:208–217

    CAS  PubMed  Google Scholar 

  • Giese A, Groschup MH, Hess B, Kretzschmar HA (1995) Neuronal cell death in scrapie-infected mice is due to apoptosis. Brain Pathol 5:213–221

    CAS  PubMed  Google Scholar 

  • Gillardon F, Wickert H, Zimmermann M (1995) Up-regulation of bax and down-regulation of bcl-2 is associated with kainate-induced apoptosis in mouse brain. Neurosci Lett 192:85–88

    CAS  PubMed  Google Scholar 

  • Goldberg YP, Nicholson DW, Rasper DM, Kalchman MA, Koide HB, Graham RK, Bromm M, Kazemi-Esfarjani P, Thornberry NA, Vaillancourt JP, Hayden MR (1996) Cleavage of huntingtin by apopain, a proapoptotic cysteine protease, is modulated by the polyglutamine tract. Nat Genet 13:442–449

    CAS  PubMed  Google Scholar 

  • Gross SS, Wolin MS (1995) Nitric oxide: pathophysiological mechanisms. Annu Rev Physiol 57:737–769

    CAS  PubMed  Google Scholar 

  • Gschwind M, Huber G (1995) Apoptotic cell death induced by beta-amyloid 1–42 peptide is cell type dependent. J Neurochem 65:292–300

    CAS  PubMed  Google Scholar 

  • Guo Q, Sopher BL, Furukawa K, Pham DG, Robinson N, Martin GM, Mattson MP (1997) Alzheimer’s presenilin mutation sensitizes neural cells to apoptosis induced by trophic factor withdrawal and amyloid beta-peptide: involvement of calcium and oxyradicals. J Neurosci 17:4212–4222

    CAS  PubMed  Google Scholar 

  • Gwag BJ, Lobner D, Koh JY, Wie MB, Choi DW (1995) Blockade of glutamate receptors unmasks neuronal apoptosis after oxygen-glucose deprivation in vitro. Neuroscience 68:615–619

    CAS  PubMed  Google Scholar 

  • Hafezi F, Steinbach JP, Marti A, Munz K, Wang Z-Q, Wagner EF, Aguzzi A, Reme CE (1997) The absence of c-fos prevents light-induced apoptotic cell death of photoreceptors in retinal degeneration in vivo. Nat Med 3:346–349

    CAS  PubMed  Google Scholar 

  • Hara H, Friedlander RM, Gagliardini V, Ayata C, Fink K, Huang Z, Shimizu-Sasamata M, Yuan J, Moskowitz MA (1997a) Inhibition of interleukin 1beta converting enzyme family proteases reduces ischemic and excitotoxic neuronal damage. Proc Natl Acad Sci USA 94:2007–2012

    CAS  PubMed  Google Scholar 

  • Hara H, Fink K, Endres M, Friedlander RM, Gagliardini V, Yuan J, Moskowitz M (1997b) Attenuation of transient focal cerebral ischemic injury in transgenic mice expressing a mutant ICE inhibitory protein. J Cereb Blood Flow Metab 17:370–375

    CAS  PubMed  Google Scholar 

  • Hartley A, Stone JM, Heron C, Cooper JM, Schapira AHV (1994) Complex I inhibitors induce dose-dependent apoptosis in PC12 cells: relevance to Parkinson’s disease. J Neurochem 63:1987–1990

    CAS  PubMed  Google Scholar 

  • Henneberry RC, Novelli A, Cox JA, Lysko PG (1989) Neurotoxicity at the N-methyl-D-aspartate receptor in energy-compromised neurons. An hypothesis for cell death in aging and disease. Ann NY Acad Sci 568:225–233

    CAS  PubMed  Google Scholar 

  • Héron A, Pollard H, Dessi F, Moreau J, Lasbennes F, Ben-Ari Y, Charriaut-Marlangue C (1993) Regional variability in DNA fragmentation after global ischemia evidenced by combined histological and gel electrophoresis observations in the rat brain. J Neurochem 61:1973–1976

    PubMed  Google Scholar 

  • Hirsch DB, Steiner JP, Dawson TM, Mammen A, Hayek E, Snyder SH (1993) Neurotransmitter release regulated by nitric oxide in PC-12 cells and brain synaptosomes. Curr Biol 3:749–754

    CAS  PubMed  Google Scholar 

  • Hirsch T, Marchetti P, Susin SA, Dallaporta B, Zamzami N, Marzo I, Geuskens M, Kroemer G (1997) The apoptosis-necrosis paradox. Apoptogenic proteases activated after mitochondrial permeability transition determine the mode of cell death. Oncogene 15:1573–1581

    CAS  PubMed  Google Scholar 

  • Hisahara S, Shoji S, Okano H, Miura M (1997) ICE/CED-3 family executes oligodendrocyte apoptosis by tumor necrosis factor. J Neurochem 69:10–20

    CAS  PubMed  Google Scholar 

  • Hooper DC, Bagasra O, Marini JC, Zborel A, Ohnishi ST, Kean R, Champion JM, Sarker AB, Bobroski L, Farber JL, Akaike T, Maeda H, Koprowski H (1997) Prevention of experimental allergic encephalomyelitis by targeting nitric oxide and peroxynitrite: implications for the treatment of multiple sclerosis. Proc Natl Acad Sci USA 94:2528–2533

    CAS  PubMed  Google Scholar 

  • Huang PL, Fishman MC (1996) Genetic analysis of nitric oxide synthase isoforms: targeted mutation in mice. J Mol Med 74:415–421

    CAS  PubMed  Google Scholar 

  • Huang Z, Huang PL, Panahian N, Dalkara T, Fishman MC, Moskowitz MA (1994) Effects of cerebral ischemia in mice deficient in neuronal nitric oxide synthase. Science 265:1883–1885

    CAS  PubMed  Google Scholar 

  • Ischiropoulos H, Zhu L, Chen J, Tsai M, Martin JC, Smith CD, Beckman JS (1992) Peroxynitrite-mediated tyrosine nitration catalyzed by superoxide dismutase. Arch Biochem Biophys 298:431–437

    CAS  PubMed  Google Scholar 

  • Ishimaru H, Katoh A, Suzuki H, Fukuta T, Kameyama T, Nabeshima T (1992) Effects of N-methyl-D-aspartate receptor antagonists on carbon monoxide-induced brain damage in mice. J Pharmacol Exp Ther 261:349–352

    CAS  PubMed  Google Scholar 

  • Ishitani R, Sunaga K, Hirano A, Saunders P, Katsube N, Chuang D-M (1996) Evidence that glyceraldehyde-3-phosphate dehydrogenase is involved in age-induced apoptosis in mature cerebellar neurons in culture. J Neurochem 66:928–935

    CAS  PubMed  Google Scholar 

  • Ishitani R, Sunaga K, Tanaka M, Aishita H, Chuang D-M (1997) Overexpression of glyceraldehyde-3-phosphate dehydrogenase is involved in low K+-induced apoptosis but not necrosis of cultured cerebellar granule cells. Mol Pharmacol 51:542–550

    CAS  PubMed  Google Scholar 

  • Islam N, Aftabuddin M, Moriwaki A, Hori Y (1995) Detection of DNA damage induced by apoptosis in the rat brain following incomplete ischemia. Neurosci Lett 188:159–162

    CAS  PubMed  Google Scholar 

  • Ito A, Horigome K (1995) Ceramide prevents neuronal programmed cell death induced by nerve growth factor deprivation. J Neurochem 65:463–466

    CAS  PubMed  Google Scholar 

  • Jacobson MD, Burne JF, Raff MC (1994) Programmed cell death and Bcl-2 protection in the absence of a nucleus. EMBO J 13:1899–1910

    CAS  PubMed  Google Scholar 

  • Jordán J, Galindo MF, Prehn JHM, Weichselbaum RR, Beckett M, Ghadge GD, Roos RP, Leiden JM, Miller RJ (1997) p53 epression induces apoptosis in hippocampal pyramidal neuron cultures. J Neurosci 17:1397–1405

    PubMed  Google Scholar 

  • Kane DJ, Örd T, Anton R, Bredesen DE (1995) Expression of bcl-2 inhibits necrotic neuronal cell death. J Neurosci Res 40:269–275

    CAS  PubMed  Google Scholar 

  • Kerr JF, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide ranging implications in tissue kinetics. Br J Cancer 26:239–247

    CAS  PubMed  Google Scholar 

  • Kharlamov E, Cagnoli CM, Atabay C, Ikonomovic S, Grayson DR, Manev H (1995) Opposite effect of protein synthesis inhibitors on potassium deficiency-induced apoptotic cell death in immature and mature neuronal cultures. J Neurochem 65:1395–1398

    CAS  PubMed  Google Scholar 

  • Kilbourn MR, Charalambous A, Frey KA, Sherman P, Higgins DSJ, Greenamyre JT (1997) Intrastriatal neurotoxin injections reduce in vitro and in vivo binding of radiolabeled rotenoids to mitochondrial complex I. J Cereb Blood Flow Metab 17:265–272

    CAS  PubMed  Google Scholar 

  • Kim T-W, Pettingell WH, Jung Y-K, Kovacs DM, Tanzi RE (1997) Alternative cleavage of Alzheimer-associated presenilins during apoptosis by a caspase-3 family protease. Science 277:373–377

    CAS  PubMed  Google Scholar 

  • Koh J-Y, Gwag BJ, Lobner D, Choi DW (1995a) Potentiated necrosis of cultured cortical neurons by neurotrophins. Science 268:573–575

    CAS  PubMed  Google Scholar 

  • Koh J-Z, Wie MB, Gwag BJ, Sensi SL, Canzoniero LMT, Demaro J, Csernansky C, Choi DW (1995b) Staurosporine-induced neuronal apoptosis. Exp Neurol 135:153–159

    CAS  PubMed  Google Scholar 

  • Krajewski S, Mai JK, Krajewska M, Sikorska M, Mossakowski MJ, Reed JC (1995) Upregulation of bax protein levels in neurons following cerebral ischemia. J Neurosci 15:6364–6376

    CAS  PubMed  Google Scholar 

  • Kruman I, Bruce-Keller AJ, Bredesen D, Waeg G, Mattson MP (1997) Evidence that 4-hydroxynonenal mediates oxidative stress-induced neuronal apoptosis. J Neurosci 17:5089–5100

    CAS  PubMed  Google Scholar 

  • Kubo T, Nonomura T, Enokido Y, Hatanaka H (1995) Brain-derived neurotrophic factor (BDNF) can prevent apoptosis of rat cerebellar granule neurons in culture. Dev Brain Res 85:249–258

    CAS  Google Scholar 

  • Künstle G, Leist M, Uhlig S, Revesz L, Feifel R, MacKenzie A, Wendel A (1997) ICE-protease inhibitors block murine liver injury and apoptosis caused by CD95 or TNF-alpha. Immunol Lett 55:5–10

    PubMed  Google Scholar 

  • Kure S, Tominaga T, Yoshimoto T, Tada K, Narisawa K (1991) Glutamate triggers internucleosomal DNA cleavage in neuronal cells. Biochem Biophys Res Commun 179:39–45

    CAS  PubMed  Google Scholar 

  • Larocca JN, Farooq M, Norton WT (1997) Induction of oligodendrocyte apoptosis by C2-ceramide. Neurochem Res 22:529–534

    CAS  PubMed  Google Scholar 

  • Lassmann H, Bancher C, Breitschopf H, Wegiel J, Bobinski M, Jellinger K, Wisniewski HM (1995) Cell death in Alzheimer’s disease evaluated by DNA fragmentation in situ. Acta Neuropathol 89:35–41

    CAS  PubMed  Google Scholar 

  • Leist M, Nicotera P (1997a) Calcium and neural death. Rev Physiol Pharmacol Biochem 132:79–125

    Google Scholar 

  • Leist M, Nicotera P (1997b) The shape of cell death. Biochem Biophys Res Commun 236:1–9

    CAS  PubMed  Google Scholar 

  • Leist M, Gantner F, Bohlinger I, Tiegs G, Germann PG, Wendel A (1995) Tumor necrosis factor-induced hepatocyte apoptosis precedes liver failure in experimental murine shock models. Am J Pathol 146:1220–1234

    CAS  PubMed  Google Scholar 

  • Leist M, Fava E, Montecucco C, Nicotera P (1997a) Peroxynitrite and NO-donors induce neuronal apoptosis by eliciting autocrine excitotoxicity. Eur J Neurosci 9:1488–1498

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Leist M, Single B, Künstle G, Volbracht C, Hentze H, Nicotera P (1997c) Apoptosis in the absence of poly-(ADP-ribose) polymerase. Biochem Biophys Res Commun 334:518–522

    Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Leist M, Volbracht C, Fava E, Nicotera P (1998) l-Methyl-4-phenylpyridinium (MPP+) induces autocrine excitotoxicity, protease activation and neuronal apoptosis. (submitted)

    Google Scholar 

  • Li Y, Chopp M, Jiang N, Yao F, Zaloga C (1995a) Temporal profile of in situ DNA fragmentation after transient middle cerebral artery occlusion in the rat. J Cereb Blood Flow Metab 15:389–397

    CAS  PubMed  Google Scholar 

  • Li Y, Chopp M, Jiang N, Zaloga C (1995b) In situ detection of DNA fragmentation after focal cerebral ischemia in mice. Mol Brain Res 28:164–168

    CAS  PubMed  Google Scholar 

  • Li Y, Chopp M, Jiang N, Zhang ZG, Zaloga C (1995c) Induction of DNA fragmentation after 10 to 120 minutes of focal cerebral ischemia in rats. Stroke 26:1252–1258

    CAS  PubMed  Google Scholar 

  • Li Y, Sharov VG, Jiang N, Zaloga C, Sabbah HN, Chopp M (1995d) Ultrastructural and light microscopic evidence of apoptosis after middle cerebral artery occlusion in the rat. Am J Pathol 146:1045–1051

    CAS  PubMed  Google Scholar 

  • Lin K-T, Xue J-Y, Nomen M, Spur B, Wong PY-K (1995) Peroxynitrite-induced apoptosis in HL-60 cells. J Biol Chem 270:16487–16490

    CAS  PubMed  Google Scholar 

  • Lindenboim L, Haviv R, Stein R (1995) Inhibition of drug-induced apoptosis by survival factors in PC12 cells. J Neurochem 64:1054–1063

    CAS  PubMed  Google Scholar 

  • Linnik MD, Miller JA, Sprinkle-Cavallo J, Mason PJ, Thompson FY, Montgomery LR, Schroeder KK (1995a) Apoptotic DNA fragmentation in the rat cerebral cortex induced by permanent middle cerebral artery occlusion. Mol Brain Res 32:116–124

    CAS  PubMed  Google Scholar 

  • Linnik MD, Zahos P, Geschwind MD, Federoff HJ (1995b) Expression of bcl-2 from a defective herpes simplex virus-1 vector limits neuronal death in focal cerebral ischemia. Stroke 26:1670–1675

    CAS  PubMed  Google Scholar 

  • Lipton SA, Rosenberg PA (1994) Excitatory amino acids as a final common pathway for neurologic disorders. New Engl J Med 330:613–622

    CAS  PubMed  Google Scholar 

  • Lipton SA, Choi Y-B, Pan Z-H, Lei SZ, Chen H-SV, Sucher NJ, Loscalzo J, Singel DJ, Stamler JS (1993) A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds. Nature 364:626–632

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Loo DT, Copani A, Pike CJ, Whittemore ER, Walencewicz AJ, Cotman CW (1993) Apoptosis is induced by beta-amyloid in cultured central nervous system neurons. Proc Natl Acad Sci USA 90:7951–7955

    CAS  PubMed  Google Scholar 

  • Louis J-C, Magal E, Takayama S, Varon S (1993) CNTF protection of oligodendrocytes against natural and tumor necrosis factor-induced death. Science 259:689–692

    CAS  PubMed  Google Scholar 

  • Lucas M, Izquierdo G, Munoz C, Solano F (1997) Internucleosomal breakdown of the DNA of brain cortex in human spongiform encephalopathy. Neurochem Int 31:241–244

    CAS  PubMed  Google Scholar 

  • Lynch T, Vasilakos JP, Raser K, Keane KM, Shivers BD (1997) Inhibition of the interleukin-1 beta converting enzyme family rescues neurons from apoptotic death. Mol Psychiatry 2:227–238

    CAS  PubMed  Google Scholar 

  • MacManus JP, Rasquinha I, Black MA, Laferriere NB, Monette R, Walker T, Morley P (1997) Glutamate-treated rat cortical neuronal cultures die in a way different from the classical apoptosis induced by staurosporine. Exp Cell Res 233:310–320

    CAS  PubMed  Google Scholar 

  • Mah SP, Zhong LT, Liu Y, Roghani A, Edwards RH, Bredesen DE (1993) The protooncogene bcl-2 inhibits apoptosis in PC12 cells. J Neurochem 60:1183–1186

    CAS  PubMed  Google Scholar 

  • Martin DP, Schmidt RE, DiStefano PS, Lowry OH, Carter JG, Johnson EM (1988) Inhibitors of protein synthesis and RNA synthesis prevent neuronal death caused by nerve growth factor deprivation. J Cell Biol 106:829–844

    CAS  PubMed  Google Scholar 

  • Martin SJ, Reutelingsperger CPM, McGahon AJ, Rader JA, van Schie, RCAA, LaFace DM, Green DR (1995) Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpressing of Bcl-2 and Abl. J Exp Med 182:1545–1556

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Martinou I, Fernandez P-A, Missotten M, White E, Allet B, Sadoul R, Martinou J-C (1995) Viral proteins E1B19K and p35 protect sympathetic neurons from cell death induced by NGF deprivation. J Cell Biol 128:201–208

    CAS  PubMed  Google Scholar 

  • Masliah E, Sisk A, Mallory M, Mucke L, Schenk D, Games D (1996) Comparison of neurodegenerative pathology in transgenic mice overexpressing V717F beta-amyloid precursor protein and Alzheimer’s disease. J Neurosci 15:5795–5811

    Google Scholar 

  • McLaurin J, D’Souza S, Stewart J, Blain M, Beaudet A, Nalbantoglu J, Antel JP (1995) Effect of tumor necrosis factor alpha and beta on human oligodendrocytes and neurons in culture. Int J Dev Neurosci 13:369–381

    CAS  PubMed  Google Scholar 

  • McQuaid S, McMahon J, Herron B, Cosby SL (1997) Apoptosis in measles virus-infected human central nervous system tissues. Neuropathol Appl Neurobiol 23:218–224

    CAS  PubMed  Google Scholar 

  • Meffert MK, Premack BA, Schulman H (1994) Nitric oxide stimulates calcium-independent synaptic vesicle release. Neuron 12:1235–1244

    CAS  PubMed  Google Scholar 

  • Meffert MK, Calakos NC, Scheller RH, Schulman H (1996) Nitric oxide modulates synaptic vesicle docking/fusion reactions. Neuron 16:1229–1236

    CAS  PubMed  Google Scholar 

  • Meldrum B, Garthwaite J (1990) Excitatory amino acid neurotoxicity and neurodegenerative disease. Trends Pharmacol Sci 11:379–387

    CAS  PubMed  Google Scholar 

  • Melino G, Bernassola F, Knight RA, Corasaniti MT, Nistico G, Finazzi-Agro A (1997) S-nitrosylation regulates apoptosis Nature 388:432–433

    CAS  Google Scholar 

  • Merrill JE, Ignarro LJ, Sherman MP, Melinek J, Lane TE (1993) Microglial cell cytotoxicity of oligodendrocytes is mediated through nitric oxide. J Immunol 151:2132–2141

    CAS  PubMed  Google Scholar 

  • Mesner PW, Winters TR, Green SH (1992) Nerve growth factor withdrawal-induced cell death in neuronal PC12 cells resembles that in sympathetic neurons. J Cell Biol 119:1669–1680

    CAS  PubMed  Google Scholar 

  • Mesner PW, Epting CL, Hegarty JL, Green SH (1995) A timetable of events during programmed cell death induced by trophic factor withdrawal from neuronal PC12 cells. J Neurosci 15:7357–7366

    CAS  PubMed  Google Scholar 

  • Middleton G, Nunez G, Davies AM (1996) Bax promotes neuronal survival and antagonises the survival effects of neurotrophic factors. Development 122:695–701

    CAS  PubMed  Google Scholar 

  • Mitchell IJ, Lawson S, Moser B, Laidlaw SM, Cooper AJ, Walkinshaw G, Waters CM (1994) Glutamate-induced apoptosis results in a loss of striatal neurons in the Parkinsonian rat. Neurosci 63:1–5

    CAS  Google Scholar 

  • Mochizuki H, Nakamura N, Nishi K, Mizuno Y (1994) Apoptosis is induced by 1-methyl-4-phenylpyridinium ion (MPP+) in ventral mesencephalic-striatal co-culture in rat. Neurosci Lett 170:191–194

    CAS  PubMed  Google Scholar 

  • Mochizuki H, Goto K, Mori H, Mizuno Y (1996) Histochemical detection of apoptosis in Parkinson’s disease. J Neurol Sci 137:120–123

    CAS  PubMed  Google Scholar 

  • Molinari M, Carafoli E (1997) Calpain: a cytosolic proteinase active at the membranes. J Membr Biol 156:1–8

    CAS  PubMed  Google Scholar 

  • Monyer H, Giffard RG, Hartley DM, Dugan LL, GMP, Choi DW (1992) Oxygen or glucose deprivation-induced neuronal injury in cortical cell cultures is reduced by tetanus toxin. Neuron 8:967–973

    CAS  PubMed  Google Scholar 

  • Morris EJ, Geller HM (1996) Induction of neuronal apoptosis by camptothecin, an inhibitor of DNA topoisomerase-I: evidence for cell cycle-independent toxicity. J Cell Biol 134:757–770

    CAS  PubMed  Google Scholar 

  • Morrison RS, Wenzel HJ, Kinoshita Y, Robbins CA, Donehower LA, Schwartzkroin PA (1996) Loss of the p53 tumor suppressor gene protects neurons from kainate-induced cell death. J Neurosci 16:1337–1345

    CAS  PubMed  Google Scholar 

  • Morrison RS, Sharma A, de Vellis J, Bradshaw RA (1986) Basic fibroblast growth factor supports the survival of cerebral cortical neurons in primary culture. Proc Natl Acad Sci USA 83:7537–7541

    CAS  PubMed  Google Scholar 

  • Müller WEG, Schröder HC, Ushijima H, Dapper J, Bormann J (1992) gp120 of HIV-1 induces apoptosis in rat cortical cell cultures: prevention by memantine. Eur J Pharmacol 226:209–214

    PubMed  Google Scholar 

  • Müller WEG, Ushijima H, Schröder HC, Forrest JMS, Schatton WFH, Rytik PG, Heffner-Lauc M (1993) Cytoprotective effect of NMDA receptor antagonists on prion protein (PrionSc)-induced toxicity in rat cortical cell cultures. Eur J Pharmacol 246:261–267

    PubMed  Google Scholar 

  • Müller WEG, Romero FJ, Perovic S, Pergande G, Pialoglou P (1997) Protection of flupirtine on beta-amyloid-induced apoptosis in neuronal cells in vitro: prevention of amyloid-induced glutathione depletion. J Neurochem 68:2371–2377

    PubMed  Google Scholar 

  • Nath R, Raser KJ, Stafford D, Hajimohammadreza I, Rosner A, Allen H, Talanian RV, Yuen P, Gilbertsen RB, Wang KKW (1996) Non-erythroid alpha-spectin breakdown by calpain and interleukin 1beta-converting-enzyme-like protease(s) in apoptotic cells: contributory roles of both protease families in neuronal apoptosis. Biochem J 319:683–690

    CAS  PubMed  Google Scholar 

  • New DR, Ma M, Epstein LG, Nath A, Gelbard HA (1997) Human immunodeficiency virus type 1 Tat protein induces death by apoptosis in primary human neuron cultures. J Neurovirol 3:168–173

    CAS  PubMed  Google Scholar 

  • Newell DW, Hsu SS, Papermaster V, Malouf AT (1993) Colchicine is selectively neurotoxic to dentate granule cells in organotypic cultures of rat hippocampus. NeuroToxicology 14:375–381

    CAS  PubMed  Google Scholar 

  • Nicholls D, Attwell D (1990) The release and uptake of excitatory amino acids. Trends Pharmacol Sci 11:462–468

    PubMed  Google Scholar 

  • Nicotera P, Leist M (1997) Energy supply and the shape of death in neurons and lymphoid cells. Cell Death Differ 4:435–442

    CAS  PubMed  Google Scholar 

  • Nicotera P, Hartzeil P, Baldi C, Svensson S-A, Bellomo G, Orrenius S (1986) Cystamine induces toxicity in hepatocytes through the elevation of cytosolic Ca2+ and the stimulation of a nonlysosomal proteolytic system. J Biol Chem 261:14628–14635

    CAS  PubMed  Google Scholar 

  • Nitatori T, Sato N, Waguri S, Karasawa Y, Araki H, Shibanai K, Kominami E, Uchiyama Y (1995) Delayed neuronal death in the CA1 pyramidal cell layer of the gerbil hippocampus following transient ischemia is apoptosis. J Neurosci 15:1001–1011

    CAS  PubMed  Google Scholar 

  • Novelli A, Reilly JA, Lysko PG, Henneberry RC (1988) Glutamate becomes neurotoxic via the N-methyl-D-aspartate receptor when intracellular energy levels are reduced. Brain Res 451:205–212

    CAS  PubMed  Google Scholar 

  • Oberhammer F, Wilson JW, Dive C, Morris ID, Hickman JA, Wakeling AE, Walker PR, Sikorska M (1993) Apoptotic death in epithelial cells: cleavage of DNA to 300 and/or 50 kb fragments prior to or in the absence of internucleosomal fragmentation. EMBO J 12:3679–3684

    CAS  PubMed  Google Scholar 

  • O’Dell TJ, Hawkins RD, Kandel ER, Arancio O (1991) Tests of the roles of two diffusible substances in long-term potentiation: evidence for nitric oxide as a possible early retrograde messenger. Proc Natl Acad Sci USA 88:11285–11289

    PubMed  Google Scholar 

  • Oka A, Belliveau MJ, Rosenberg PA, Volpe JJ (1993) Vulnerability of Oligodendroglia to glutamate: pharmacology, mechanisms, and prevention. J Neurosci 13:1441–1453

    CAS  PubMed  Google Scholar 

  • Oppenheim RW, Houenou LJ, Johnson JE, Lin L-FH, Li L, Lo AC, Newsome AL, Prevette DM, Wang S (1995) Developing motor neurons rescued from programmed and axotomy-induced cell death by GDNF. Nature 373:344–346

    CAS  PubMed  Google Scholar 

  • Pang Z, Geddes JW (1997) Mechanisms of cell death induced by the mitochondrial toxin 3-nitropropionic acid: acute excitotoxic necrosis and delayed apoptosis. J Neurosci 17:3064–3073

    CAS  PubMed  Google Scholar 

  • Park DS, Morris EJ, Greene LA, Geller HM (1997) G1/S cell cycle blockers and inhibitors of cyclin-dependent kinases suppress camptothecin-induced neuronal apoptosis. J Neurosci 17:1256–1270

    CAS  PubMed  Google Scholar 

  • Patterson PH (1995) Cytokines in Alzheimer’s disease and multiple sclerosis. Curr Opin Neurobiol 5:642–646

    CAS  PubMed  Google Scholar 

  • Petito CK, Roberts B (1995) Evidence of apoptotic cell death in HIV encephalitis. Am J Pathol 146:1121–1130

    CAS  PubMed  Google Scholar 

  • Piacentini M, Annicchiarico-Petruzzelli M, Oliverio S, Piredda L, Biedler JL, Melino G (1992) Phenotype-specific “tissue” transglutaminase regulation in human neuroblastoma cells in response to retinoic acid: correlation with cell death by apoptosis. Int J Cancer 52:271–278

    CAS  PubMed  Google Scholar 

  • Pollard H, Cantagrel S, Charriaut-Marlangue C, Moreau J, Ari YB (1994a) Apoptosis associated DNA fragmentation in epileptic brain damage. NeuroReport 5:1053–1055

    CAS  PubMed  Google Scholar 

  • Pollard H, Charriaut-Marlangue C, Centagrel A, Represa A, Robain O, Moreau J, Ben-Ari Y (1994b) Kainate-induced apoptotic cell death in hippocampal neurons. Neuroscience 63:7–18

    CAS  PubMed  Google Scholar 

  • Portera-Cailliau C, Hedreen JC, Price DL, Koliatsos VE (1995) Evidence for apoptotic cell death in Huntington disease and excitotoxic animal models. J Neurosci 15:3775–3787

    CAS  PubMed  Google Scholar 

  • Portera-Cailliau C, Price DL, Martin LJ (1997a) Excitotoxic neuronal death in the immature brain is an apoptosis-necrosis morphological continuum. J Comp Neurol 378:70–87

    CAS  PubMed  Google Scholar 

  • Portera-Cailliau C, Price DL, Martin LJ (1997b) Non-NMDA and NMDA receptor-mediated excitotoxic neuronal deaths in adult brain are morphologically distinct: further evidence for an apoptosis-necrosis continuum. J Comp Neurol 378:88–104

    CAS  PubMed  Google Scholar 

  • Rabizadeh S, Oh J, Zhong L-T, Yang J, Bitler CM, Butcher LL, Bredesen DE (1993) Induction of apoptosis by the low-affinity NGF receptor. Science 261:345–348

    CAS  PubMed  Google Scholar 

  • Radi R, Beckmann JS, Bush KM, Freeman BA (1991) Peroxynitrite oxidation of sulfhydryls. The cytotoxic potential of superoxide and nitric oxide. J Biol Chem 266:4244–4250

    CAS  PubMed  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

    CAS  PubMed  Google Scholar 

  • Ratan RR, Murphy TH, Baraban JM (1994) Oxidative stress induces apoptosis in embryonic cortical neurons. J Neurochem 62:376–379

    CAS  PubMed  Google Scholar 

  • Rink A, Fung K-M, Trojanowski JQ, Lee VM-Y, Neugebauer E, Mcintosh TK (1995) Evidence of apoptotic cell death after experimental traumatic brain injury in the rat. Am J Pathol 147:1575–1583

    CAS  PubMed  Google Scholar 

  • Rosomoff HL, Kochanek PM, Clark R, DeKosky ST, Ebmeyer U, Grenvik AN, Marion DW, Obrist W, Palmer AM, Safer P, White RJ (1996) Resuscitation from severe brain trauma. Crit Care Med 24:S48-S56

    Google Scholar 

  • Rossi AD, Viviani B, Zhivotovsky B, Manzo L, Orrenius S, Vahter M, Nicotera P (1997) Inorganic mercury modifies calcium2+- signalling, triggers apoptosis and potentiates NMDA toxicity in neural cells. Cell Death Differ 4:317–324

    CAS  PubMed  Google Scholar 

  • Rothman S (1984) Synaptic release of excitatory amino acid neurotransmitter mediates anoxic neuronal death. J Neurosci 4:1884–1891

    CAS  PubMed  Google Scholar 

  • Ruggiero V, Johnson SE, Baglioni C (1987) Protection from tumor necrosis factor cytotoxicity by protease inhibitors. Cell Immunol 107:317–325

    CAS  PubMed  Google Scholar 

  • Sadoul R, Fernandez P-A, Quiquerez A-L, Martinou I, Maki M, Schröter M, Becherer JD, Irmler M, Tschopp J, Martinou J-C (1996a) Involvement of the proteasome in the programmed cell death of NGF-deprived sympathetic neurons. EMBO J 15:3845–3852

    CAS  PubMed  Google Scholar 

  • Sadoul R, Quiquerez A-L, Martinou I, Fernandez PA, Martinou J-C (1996b) p53 protein in sympathetic neurons: cytoplasmic localization and no apparent function in apoptosis. J Neurosci Res 43:594–601

    CAS  PubMed  Google Scholar 

  • Sagot Y, Dubois-Dauphin M, Tan SA, de Bilbao F, Aebischer P, Martinou JC, Kato AC (1995) Bcl-2 overexpression prevents motoneuron cell body loss but not axonal degeneration in a mouse model of a neurodegenerative disease. J Neurosci 15:7727–7733

    CAS  PubMed  Google Scholar 

  • Saido TC, Sorimachi H, Suzuki K (1994) Calpain: new perspectives in molecular diversity and physiological-pathological involvement. FASEB J 8:814–822

    CAS  PubMed  Google Scholar 

  • Sakhi S, Bruce A, Sun N, Tosso G, Baudry M, Schreiber SS (1994) p53 induction is associated with neuronal damage in the central nervous system. Proc Natl Acad Sci USA 91:7525–7529

    CAS  PubMed  Google Scholar 

  • Sandani AF, Dawson TM, Dawson VL (1997) Nitric oxide synthase in models of focal ischemia. Stroke 28:1283–1288

    Google Scholar 

  • Sandberg M, Butcher SP, Hagberg H (1986) Extracellular overflow of neuroactive amino acids during severe insulin-induced hypoglycemia: in vivo dialysis of the rat hippocampus. J Neurochem 47:178–184

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Savill J, Fadok V, Henson P, Haslett C (1993) Phagocyte recognition of cells undergoing apoptosis. Immunol Today 14:131–136

    CAS  PubMed  Google Scholar 

  • Schinder AF, Olson EC, Spitzer NC, Montai M (1996) Mitochondrial dysfunction is a primary event in glutamate neurotoxicity. J Neurosci 16:6125–6133

    CAS  PubMed  Google Scholar 

  • Schulz JB, Matthews RT, Jenkins BG, Ferrante RJ, Siwek D, Henshaw DR, Cipolloni PB, Mecocci P, Kowall NW, Rosen BR, Beal MF (1995) Blockade of neuronal nitric oxide synthase protects against excitotoxicity in vivo. J Neurosci 15:8419–8429

    CAS  PubMed  Google Scholar 

  • Schulz JB, Huang PL, Matthews RT, Passov D, Fishman MC, Beal MF (1996a) Striatal malonate lesions are attenuated in neuronal nitric oxide synthase knockout mice. J Neurochem 67:430–433

    CAS  PubMed  Google Scholar 

  • Schulz JB, Weiler M, Klockgether T (1996b) Potassium deprivation-induced apoptosis of cerebellar granule neurons: a sequential requirement for new mRNA and protein synthesis, ICE-like protease activity, and reactive oxygen species. J Neurosci 16:4696–4706

    CAS  PubMed  Google Scholar 

  • Schwartz LM, Osborne BA (1993) Programmed cell death, apoptosis and killer genes. Immunol Today 14:582–590

    CAS  PubMed  Google Scholar 

  • Searle J, Kerr JFR, Bishop CJ (1982) Necrosis and apoptosis: distinct modes of cell death with fundamentally different significance. Pathol Ann 17:229–259

    Google Scholar 

  • Sendtner M, Schmalbruch H, Stöckli KA, Carroll P, Kreutzberg GW, Thoenen H (1992) Ciliary neurotrophic factor prevents degeneration of motor neurons in mouse mutant progressive motor neuronopathy. Nature 358:502–504

    CAS  PubMed  Google Scholar 

  • Sheehan JP, Palmer PE, Helm GA, Tuttle JB (1997) MPP+ induced apoptotic cell death in SH-SY5Y neuroblastoma cells: an electron microscope study. J Neurosci Res 48:226–237

    CAS  PubMed  Google Scholar 

  • Shimizu S, Eguchi Y, Kamiike W, Itoh Y, Hasegawa J-I, Yamabe K, Otsuki Y, Matsuda H, Tsujimoto Y (1996a) Induction of apoptosis as well as necrosis by hypoxia and predominant prevention of apoptosis by Bcl-2 and Bcl-xL. Cancer Res 56:2161–2166

    CAS  PubMed  Google Scholar 

  • Shimizu S, Eguchi Y, Kamiike W, Waguri S, Uchiyama Y, Matsuda H, Tsujimoto Y (1996b) Retardation of chemical hypoxia-induced necrotic cell death by Bcl-2 and ICE inhibitors: possible involvement of common mediators in apoptotic and necrotic signal transductions. Oncogene 12:2045–2050

    CAS  PubMed  Google Scholar 

  • Sloviter RS, Dean E, Sollas AL, Goodman JH (1996) Apoptosis and necrosis induced in different hippocampal neuron populations by repetitive perforant path stimulation in the rat. J Comp Neurol 366:516–533

    CAS  PubMed  Google Scholar 

  • Smale G, Nichols NR, Brady DR, Finch CE, Horton jr. WE (1995) Evidence for apoptotic cell death in Alzheimer’s disease. Exp Neurol 133:225–230

    CAS  PubMed  Google Scholar 

  • Snyder SH (1996) No NO prevents Parkinsonism. Nat Med 2:965–966

    CAS  PubMed  Google Scholar 

  • Squier MKT, Miller ACK, Malkinson AM, Cohen JJ (1994) Calpain activation in apoptosis. J Cell Physiol 159:229–237

    CAS  PubMed  Google Scholar 

  • Srinivasan A, Foster LM, Testa M-P, Örd T, Keane RW, Bredesen DE, Kayalar C (1996) Bcl-2 expression in neuronal cells blocks activation of ICE/CED-3 family proteases during apoptosis. J Neurosci 16:5654–5660

    CAS  PubMed  Google Scholar 

  • Srivastava R, Brouillet E, Beal MF, Storey E, Hyman BT (1993) Blockade of 1-methyl-4-phenylpyridinium ion (MPP+) nigral toxicity in the rat by prior decortication or MK-801 treatment: a stereological estimate of neuronal loss. Neurobiol Aging 14:295–301

    CAS  PubMed  Google Scholar 

  • Stamler JS (1994) Redox signaling: nitrosylation and related target interactions of nitric oxide. Cell 78:931–936

    CAS  PubMed  Google Scholar 

  • Stamler JS, Simon DI, Osborne JA, Mullins ME, Jaraki O, Michel T, Singel DJ, Loscalzo J (1992) S-nitrosylation of proteins with nitric oxide: synthesis and characterization of biologically active compounds. Proc Natl Acad Sci USA 89:444–448

    CAS  PubMed  Google Scholar 

  • Stamler JS, Jia L, Eu JP, McMahon TJ, Demchenko IT, Bonaventura J, Gernert K, Piantadosi CA (1997) Blood flow regulation by S-nitrosohemoglobin in the physiological oxygen gradient. Science 276:2034–2037

    CAS  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. Dissociation from apoptosis. J Biol Chem 271:30663–30671

    CAS  PubMed  Google Scholar 

  • Su JH, Anderson AJ, Cummings BJ, Cotman CW (1994) Immunohistochemical evidence for apoptosis in Alzheimer’s disease. NeuroReport 5:2529–2533

    CAS  PubMed  Google Scholar 

  • Subramanian T, Tarodi B, Chinnadurai G (1995) p53-independent apoptotic and necrotic cell deaths induced by adenovirus infection: suppression by E1B 19K and Bcl-2 proteins. Cell Growth Differ 6:131–137

    CAS  PubMed  Google Scholar 

  • Szatkowski M, Attwell D (1994) Triggering and execution of neuronal death in brain ischaemia: two phases of glutamate release by different mechanisms. Trends Neurosci 17:359–365

    CAS  PubMed  Google Scholar 

  • Tanabe H, Eguchi Y, Kamada S, Martinou J-C, Tsujimoto Y (1997) Susceptibility of cerebellar granule neurons derived from bcl-2-deficient and transgenic mice to cell death. Eur J Neurosci 9:848–856

    CAS  PubMed  Google Scholar 

  • Thomas LB, Gates DJ, Richfield EK, O’Brien TF, Schweitzer JB, Steindler DA (1995) DNA end labeling (TUNEL) in Huntington’s disease and other neuropathological conditions. Exp Neuro 133:265–272

    CAS  Google Scholar 

  • Thompson CB (1995) Apoptosis in the pathogenesis and treatment of disease. Science 267:1456–1462

    CAS  PubMed  Google Scholar 

  • Trapp BD, Nishiyama A, Cheng D, Macklin W (1997) Differentiation and death of premyelinating oligodendrocytes in developing rodent brain. J Cell Biol 137:459–468

    CAS  PubMed  Google Scholar 

  • Troost D, Aten J, Morsink F, de Jong JM (1995) Apoptosis in amyotrophic lateral sclerosis is not restricted to motor neurons. Bcl-2 expression is increased in unaffected post-central gyrus. Neuropathol Appl Neurobiol 21:498–504

    CAS  PubMed  Google Scholar 

  • Troy CM, Shelanski ML (1994) Down-regulation of copper/zinc superoxide dismutase causes apoptotic death in PC12 neuronal cells. Proc Natl Acad Sci 91:6384–6387

    CAS  PubMed  Google Scholar 

  • Troy CM, Derossi D, Prochiantz A, Greene LA, Shelanski ML (1996a) Downregulation of Cu/Zn superoxide dismutase leads to cell death via the nitric oxide-peroxynitrite pathway. J Neurosci 18:253–261

    Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Turski L, Bressler K, Rettig K-J, Löschmann P-A, Wachtel H (1991) Protection of substantia nigra from MPP+ neurotoxicity by N-methyl-D-aspartate antagonists. Nature 349:414–418

    CAS  PubMed  Google Scholar 

  • Vanags DM, Pörn-Ares MI, Coppola S, Burgess DH, Orrenius S (1996) Protease involvement in fodrin cleavage and phosphatidylserine exposure in apoptosis. J Biol Chem 271:31075–31085

    CAS  PubMed  Google Scholar 

  • Vartanian T, Li Y, Zhao M, Stefansson K (1995) Interferon-gamma-induced oligodendrocyte cell death: implications for the pathogenesis of multiple sclerosis. Mol Med 1:732–743

    CAS  PubMed  Google Scholar 

  • Vaux DL, Whitney D, Weissman IL (1996) Activation of physiological cell death mechanisms by a necrosis-causing agent. Microsc Res Tech 34:259–266

    CAS  PubMed  Google Scholar 

  • Villalba M, Bockaert J, Journot L (1997) Concomitant induction of apoptosis and necrosis in cerebellar granule cells following serum and potassium withdrawal. NeuroReport 8:981–985

    CAS  PubMed  Google Scholar 

  • Viviani B, Rossi AD, Chow SC, Nicotera P (1995) Organotin compounds induce calcium overload and apoptosis in PC12 cells. Neuro Toxicol 16:19–26

    CAS  Google Scholar 

  • von Bartheld CS, Byers MR, Williams R, Bothwell M (1996) Anterograde transport of neurotrophins and axodendritic transfer in the developing visual system. Nature 379:830–833

    Google Scholar 

  • Walker PR, Kokileva L, LeBlanc J, Sikorska M (1993) Detection of the initial stages of DNA fragmentation in apoptosis. BioTech 15:1032–1040

    CAS  Google Scholar 

  • Wallace DC, Shoffner JM, Trounce I, Brown MD, Ballinger SW, Corral-Debrinski M, Horton T, Jun AS, Lott MT (1995) Mitochondrial DNA mutations in human degenerative diseases and aging. Biochim Biophys Acta 1271:141–151

    PubMed  Google Scholar 

  • Wang KKW, Yuen P-W (1997) Development and therapeutic potential of calpain inhibitors. Adv Pharmacol 37:117–153

    CAS  PubMed  Google Scholar 

  • Wang Z-Q, Auer B, Stingl L, Berghammer H, Haidacher D, Schweiger M, Wagner EF (1995) Mice lacking ADPRT and poly(ADP-ribosyl)ation develop normally but are susceptible to skin disease. Genes Dev 9:509–520

    CAS  PubMed  Google Scholar 

  • Watt JA, Pike CJ, Walencewicz-Wasserman AJ, Cotman CW (1994) Ultrastructural analysis of beta-amyloid-induced apoptosis in cultured hippocampal neurons. Brain Res 661:147–156

    CAS  PubMed  Google Scholar 

  • Wieloch T (1985) Hypoglycemia-induced neuronal damage prevented by an N-methyl-D- aspartate antagonist. Science 230:681–683

    CAS  PubMed  Google Scholar 

  • Wood KA, Youle RJ (1995) The role of free radicals and p53 in neuron apoptosis in vivo. J Neurosci 15:5851–5857

    CAS  PubMed  Google Scholar 

  • Wyllie AH (1980) Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature 284:555–556

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Xiang H, Hochman DW, Saya H, Fujiwara T, Schwartzkroin PA, Morrison RS (1996) Evidence for p53-mediated modulation of neuronal viability. J Neurosci 16:6753–6765

    CAS  PubMed  Google Scholar 

  • Xiang J, Chao DT, Korsmeyer SJ (1997) BAX-induced cell death may not require interleukin 1 beta-converting enzyme-like proteases. Proc Natl Acad Sci USA 93:14559–14563

    Google Scholar 

  • Yamatsuji T, Matsui T, Okamoto T, Komatsuzaki K, Takeda S, Fukumoto H, Iwatsubo T, Suzuki N, Asami-Odaka A, Ireland S, Kinane TB, Giambarella U, Nishimoto I (1996) G protein-mediated neuronal DNA fragmentation induced by familial Alzheimer’s disease-associated mutants of APP. Science 272:1349–1352

    CAS  PubMed  Google Scholar 

  • Yan G-M, Lin S-Z, Irwin RP, Paul SM (1995) Activation of G proteins bidirectionally affects apoptosis of cultured cerebellar granule neurons. J Neurochem 65:2425–2431

    CAS  PubMed  Google Scholar 

  • Yuan J, Horvitz HR (1990) The Caenorhabditis elegans genes ced-3 and ced-4 act cell autonomously to cause programmed cell death. Dev Biol 138:33–41

    CAS  PubMed  Google Scholar 

  • Zajicek JP, Wing M, Scolding NJ, Compston DAS (1992) Interactions between oligodendrocytes and microglia. A major role for complement and tumour necrosis factor in oligodendrocyte adherence and killing. Brain 115:1611–1631

    PubMed  Google Scholar 

  • Zeevalk GD, Derr-Yellin E, Nicklas WJ (1995a) NMDA receptor involvement in toxicity to dopamine neurons in vitro caused by the succinate dehydrogenase inhibitor 3-nitropropionic acid. J Neurochem 64:455–458

    CAS  PubMed  Google Scholar 

  • Zeevalk GD, Derr-Yellin E, Nicklas WJ (1995b) Relative vulnerability of dopamine and GABA neurons in mesencephalic culture to inhibition of succinate dehydrogenase by malonate and 3-nitropropionic acid and protection by NMDA receptor blockade. J Pharmacol Exp Ther 275:1124–1130

    CAS  PubMed  Google Scholar 

  • Zhang J, Snyder SH (1995) Nitric oxide in the nervous system. Annu Rev Pharmacol Toxicol 35:213–233

    CAS  PubMed  Google Scholar 

  • Zhang J, Dawson VL, Dawson TM, Snyder SH (1994) Nitric oxide activation of poly(ADP-ribose) synthetase in neurotoxicity. Science 263:687–689

    CAS  PubMed  Google Scholar 

  • Zhong L-T, Sarafian T, Kane DJ, Charles AC, Mah SP, Edwards RH, Bredesen DE (1993) Bcl-2 inhibits death of central neural cells induced by multiple agents. Proc Natl Acad Sci USA 90:4533–4537

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Faculty of Biology, University of Konstanz, Box X911, Universitäts Strasse 10, 78457, Konstanz, Germany

    Marcel Leist (Chair of Molecular Toxicology) & Pierluigi Nicotera (Chair of Molecular Toxicology)

Authors
  1. Marcel Leist
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pierluigi Nicotera
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science, P. O. Box 14, Rundle Mall, Adelaide, SA, 5000, Australia

    Sharad Kumar

Rights and permissions

Reprints and permissions

Copyright information

© 1998 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Leist, M., Nicotera, P. (1998). Apoptosis Versus Necrosis: The Shape of Neuronal Cell Death. In: Kumar, S. (eds) Apoptosis: Mechanisms and Role in Disease. Results and Problems in Cell Differentiation, vol 24. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-69185-3_6

Download citation

  • DOI: https://doi.org/10.1007/978-3-540-69185-3_6

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-21625-5

  • Online ISBN: 978-3-540-69185-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation