Prospects for antiapoptotic drug therapy of neurodegenerative diseases

Progress in Neuro-Psychopharmacology and Biological Psychiatry

Volumn 27, Issue 2, 2003, Pages 303-321

  Waldmeier, Peter C ^a  

^a NOVARTIS PHARMA AG   (Switzerland)

Author keywords

Alzheimer's disease; Amyotrophic lateral sclerosis; Animal models; Apoptosis; Apoptotic pathways; Cerebral ischemia; Neurodegenerative diseases; Parkinson's disease; Small antiapoptotic molecules; Spinal cord injury; Stroke; Traumatic brain injury

Indexed keywords

ANTIOXIDANT; ANTIPARKINSON AGENT; APOPTOTIC PROTEASE ACTIVATING FACTOR 1; CEP 1347; CGP 3466B; CPI 1189; FLUPIRTINE; K 252A; PROTEIN BCL 2; PROTEIN INHIBITOR; PROTEIN P53; RASAGILINE; TCH 346;

ALZHEIMER DISEASE; AMYOTROPHIC LATERAL SCLEROSIS; ANIMAL CELL; APOPTOSIS; BRAIN INJURY; BRAIN ISCHEMIA; BRAIN NERVE CELL; CELL FUNCTION; CLINICAL TRIAL; DISEASE COURSE; DRUG EFFECT; HUMAN; HUMAN CELL; MITOCHONDRION; MOLECULAR BIOLOGY; NONHUMAN; OXIDATIVE STRESS; PARKINSON DISEASE; PATHOGENESIS; PROTEIN FAMILY; REVIEW; RISK ASSESSMENT; SPINE INJURY; TOXICITY TESTING;

EID: 0037377189     PISSN: 02785846     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0278-5846(03)00025-3     Document Type: Review

References (203)

1. Agid Y. Le viellissement, la maladie et la mort des cellules nerveuses. Bull. Acad. Med. 179:1995;1193-1203.
2. Amar A.P., Levy M.L. Pathogenesis and pharmacological strategies for mitigating secondary damage in acute spinal cord injury. Neurosurgery. 44:1999;1027-1039.
3. Andreassen O.A., Dedeoglu A., Friedlich A., Ferrante K.L., Hughes D., Szabo C., Beal M.F. Effects of an inhibitor of poly(ADP-ribose) polymerase, desmethylselegiline, trientine, and lipoic acid in transgenic ALS mice. Exp. Neurol. 168:2001;419-424.
4. Andringa G., Cools A.R. The neuroprotective effects of CGP 3466B in the best in vivo model of Parkinson's disease, the bilaterally MPTP-treated rhesus monkey. J. Neural Transm., Suppl. 2000;215-225.
5. Andringa G., van Oosten R.V., Unger W., Hafmans T.G., Veening J., Stoof J.C., Cools A.R. Systemic administration of the propargylamine CGP 3466B prevents behavioural and morphological deficits in rats with 6-hydroxydopamine-induced lesions in the substantia nigra. Eur. J. Neurosci. 12:2000;3033-3043.
6. Arrowsmith J.E., Grocott H.P., Reves J.G., Newman M.F. Central nervous system complications of cardiac surgery. Br. J. Anaesth. 84:2000;378-393.
7. Azzouz M., Hottinger A., Paterna J.C., Zurn A.D., Aebischer P., Büeler H. Increased motoneuron survival and improved neuromuscular function in transgenic ALS mice after intraspinal injection of an adeno-associated virus encoding bcl-2. Hum. Mol. Genet. 9:2000;803-811.
8. Barinaga M. Is apoptosis key in Alzheimer's disease? Science. 281:1998;1303-1304.
9. Bassi L., Carloni M., Fonti E., Palma D.L.P., Meschini R., Palitti F. Pifithrin-alpha, an inhibitor of p53, enhances the genetic instability induced by etoposide (VP16) in human lymphoblastoid cells treated in vitro. Mutat. Res. 499:2002;163-176.
10. Behl C. Apoptosis and Alzheimer's disease. J. Neural Transm. 107:2000;1325-1344.
11. Berry M.D., Boulton A.A. Glyceraldehyde-3-phosphate dehydrogenase and apoptosis. J. Neurosci. Res. 60:2000;150-154.
12. Betarbet R., Sherer T.B., MacKenzie G., Garcia-Osuna M., Panov A.V., Greenamyre J.T. Chronic systemic pesticide exposure reproduces features of Parkinson's disease. Nat. Neurosci. 3:2000;1301-1306.
13. Bezard E., Dovero S., Bioulac B., Gross C. Effects of different schedules of MPTP administration on dopaminergic neurodegeneration in mice. Exp. Neurol. 148:1997;288-292.
14. Bjugstad K.B., Flitter W.D., Garland W.A., Su G.C., Arendash G.W. Preventive actions of a synthetic antioxidant in a novel animal model of AIDS dementia. Brain Res. 795:1998;349-357.
15. Block F., Pergande G., Schwarz M. Flupirtine reduces functional deficits and neuronal damage after global ischemia in rats. Brain Res. 754:1997;279-284.
16. Blum D., Torch S., Lambeng N., Nissou M.F., Benabid A.L., Sadoul R., Verna J.M. Molecular pathways involved in the neurotoxicity of 6-OHDA, dopamine and MPTP: contribution to the apoptotic theory in Parkinson's disease. Prog. Neurobiol. 65:2001;135-172.
17. Boka G., Anglade P., Wallach D., Javoy-Agid F., Agid Y., Hirsch E.C. Immunocytochemical analysis of tumor necrosis factor and its receptors in Parkinson's disease. Neurosci. Lett. 172:1994;151-154.
18. Bondolfi L., Calhoun M., Ermini F., Kuhn H.G., Wiederhold K.H., Walker L., Staufenbiel M., Jucker M. Amyloid-associated neuron loss and gliogenesis in the neocortex of amyloid precursor protein transgenic mice. J. Neurosci. 22:2002;515-522.
19. Borasio G.D., Horstmann S., Anneser J.M., Neff N.T., Glicksman M.A. CEP-1347/KT7515, a JNK pathway inhibitor, supports the in vitro survival of chick embryonic neurons. NeuroReport. 9:1998;1435-1439.
20. Borchelt D.R., Ratovitski T., van Lare J., Lee M.K., Gonzales V., Jenkins N.A., Copeland N.G., Price D.L., Sisodia S.S. Accelerated amyloid deposition in the brains of transgenic mice coexpressing mutant presenilin 1 and amyloid precursor proteins. Neuron. 19:1997;939-945.
21. Boulton A.A. Symptomatic and neuroprotective properties of the aliphatic propargylamines. [Review, 37 refs] Mech. Ageing Dev. 111:1999;201-209.
22. Boulton A.A., Yu P.H., Davis B.A., Paterson I.A., Li X.M., Juorio A.V., Durden D.A., Dyck L.E. Aliphatic N-methylpropargylamines: monoamine oxidase-B inhibitors and antiapoptotic drugs. Adv. Pharmacol. 42:1998;308-311.
23. Bozyczko-Coyne D., O'Kane T.M., Wu Z.L., Dobrzanski P., Murthy S., Vaught J.L., Scott R.W. CEP-1347/KT-7515, an inhibitor of SAPK/JNK pathway activation, promotes survival and blocks multiple events associated with Aβ-induced cortical neuron apoptosis. J. Neurochem. 77:2001;849-863.
24. Büki A., Okonkwo D.O., Povlishock J.T. Postinjury cyclosporin A administration limits axonal damage and disconnection in traumatic brain injury. J. Neurotrauma. 16:1999;511-521.
25. Büki A., Okonkwo D.O., Wang K.K., Povlishock J.T. Cytochrome c release and caspase activation in traumatic axonal injury. J. Neurosci. 20:2000;2825-2834.
26. Bunz F. Cell death and cancer therapy. Curr. Op. Pharmacol. 1:2001;337-341.
27. Carlile G.W., Chalmers-Redman R.M.E., Tatton N.A., Pong A., Tatton W.G. Reduced apoptosis after NGF and serum withdrawal: conversion of tetrameric glyceraldehyde-3-phosphate dehydrogenase to a dimer. Mol. Pharmacol. 57:2000;2-12.
28. Chen R.W., Saunders P.A., Wei H.F., Li Z.W., Seth P., Chuang D.M. Involvement of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and p53 in neuronal apoptosis: evidence that GAPDH is upregulated by p53. J. Neurosci. 19:1999;9654-9662.
29. Cho K.J., Chung Y.H., Shin C.M., Shin D.H., Kim Y.S., Gurney M.E., Lee K.W., Cha C.I. Reactive astrocytes express p53 in the spinal cord of transgenic mice expressing a human Cu/Zn SOD mutation. NeuroReport. 10:1999;3939-3943.
30. Clark R.S., Kochanek P.M., Chen M., Watkins S.C., Marion D.W., Chen J., Hamilton R.L., Loeffert J.E., Graham S.H. Increases in Bcl-2 and cleavage of caspase-1 and caspase-3 in human brain after head injury. FASEB J. 13:1999;813-821.
31. Clark R.S., Kochanek P.M., Watkins S.C., Chen M., Dixon C.E., Seidberg N.A., Melick J., Loeffert J.E., Nathaniel P.D., Jin K.L., Graham S.H. Caspase-3 mediated neuronal death after traumatic brain injury in rats. J. Neurochem. 74:2000;740-753.
32. Cotman C.W. Apoptosis decision cascades and neuronal degeneration in Alzheimer's disease. Neurobiol. Aging. 19:1998;S29-S32. (Suppl.).
33. Crowe M.J., Bresnahan J.C., Shuman S.L., Masters J.N., Beattie M.S. Apoptosis and delayed degeneration after spinal cord injury in rats and monkeys. Nature Med. 3:1997;73-76.
34. Crumrine R.C., Thomas A.L., Morgan P.F. Attenuation of p53 expression protects against focal ischemic damage in transgenic mice. J. Cereb. Blood Flow Metab. 14:1994;887-891.
35. Culmsee C., Zhu X.X., Yu Q.S., Chan S.L., Camandola S., Guo Z.H., Greig N.H., Mattson M.P. A synthetic inhibitor of p53 protects neurons against death induced by ischemic and excitotoxic insults, and amyloid β-peptide. J. Neurochem. 77:2001;220-228.
36. Cyr M., Calon F., Morissette M., Di Paolo T. Estrogenic modulation of brain activity: implications for schizophrenia and Parkinson's disease. J. Psychiatr. Neurosci. 27:2002;12-27.
37. De Bilbao F., Guarin E., Nef P., Vallet P., Giannakopoulos P., Dubois-Dauphin M. Cell death is prevented in thalamic fields but not in injured neocortical areas after permanent focal ischaemia in mice overexpressing the anti-apoptotic protein Bcl-2. Eur. J. Neurosci. 12:2000;921-934.
38. De la Monte S.M., Sohn Y.K., Ganju N., Wands J.R. P53- and CD95-associated apoptosis in neurodegenerative diseases. Lab. Invest. 78:1998;401-411.
39. DiCamillo A.M., Neff N.T., Carswell S., Haun F.A. Chronic sparing of delayed alternation performance and choline acetyltransferase activity by CEP-1347/KT-7515 in rats with lesions of nucleus basalis magnocellularis. Neuroscience. 86:1998;473-483.
40. Dirnagl U., Iadecola C., Moskowitz M.A. Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci. 22:1999;391-397.
41. Doble A. The pharmacology and mechanism of action of riluzole. Neurology. 47:1996;S233-S241.
42. Dumont R.J., Okonkwo D.O., Verma S., Hurlbert R.J., Boulos P.T., Ellegala D.B., Dumont A.S. Acute spinal cord injury: part I. Pathophysiologic mechanisms. Clin. Neuropharmacol. 24:2001;254-264.
43. Dumont R.J., Verma S., Okonkwo D.O., Hurlbert R.J., Boulos P.T., Ellegala D.B., Dumont A.S. Acute spinal cord injury: part II. Contemporary pharmacotherapy. Clin. Neuropharmacol. 24:2001;265-279.
44. Ekegren T., Grundstrom E., Lindholm D., Aquilonius S.M. Upregulation of Bax protein and increased DNA degradation in ALS spinal cord motor neurons. Acta Neurol. Scand. 100:1999;317-321.
45. Eldadah B.A., Faden A.I. Caspase pathways, neuronal apoptosis, and CNS injury. J. Neurotrauma. 17:2000;811-829.
46. Embacher N., Kaufmann W.A., Beer R., Maier H., Jellinger K.A., Poewe W., Ransmayr G. Apoptosis signals in sporadic amyotrophic lateral sclerosis: an immunocytochemical study. Acta Neuropathol. 102:2001;426-434.
47. Emery E., Aldana P., Bunge M.B., Puckett W., Srinivasan A., Keane R.W., Bethea J., Levi A.D. Apoptosis after traumatic human spinal cord injury. J. Neurosurg. 89:1998;911-920.
48. Emilien G., Maloteaux J.M., Beyreuther K., Masters C.L. Alzheimer disease: mouse models pave the way for therapeutic opportunities. Arch. Neurol. 57:2000;176-181.
49. Endres M., Namura S., Skimizu-Sasamata M., Waeber C., Zhang L., Gómez-Isla T., Hyman B.T., Moskowitz M.A. Attenuation of delayed neuronal death after mild focal ischemia in mice by inhibition of the caspase family. J. Cereb. Blood Flow Metab. 18:1998;238-247.
50. Ertel W., Keel M., Stocker R., Imhof H.G., Leist M., Steckholzer U., Tanaka M., Trentz O., Nagata S. Detectable concentrations of Fas ligand in cerebrospinal fluid after severe head injury. J. Neuroimmunol. 80:1997;93-96.
51. Ferri K.F., Kroemer G. Organelle-specific initiation of cell death pathways. Nat. Cell Biol. 3:2001;E255-E263.
52. Glicksman M.A., Chiu A.Y., Dionne C.A., Harty M., Kaneko M., Murakata C., Oppenheim R.W., Prevette D., Sengelaub D.R., Vaught J.L., Neff N.T. CEP-1347/KT7515 prevents motor neuronal programmed cell death and injury-induced dedifferentiation in vivo. J. Neurobiol. 35:1998;361-370.
53. Gomez-Isla T., Price J.L., McKeel D.W. Jr., Morris J.C., Growdon J.H., Hyman B.T. Profound loss of layer II entorhinal cortex neurons occurs in very mild Alzheimer's disease. J. Neurosci. 16:1996;4491-4500.
54. Gonzalez de Aguilar J.L., Gordon J.W., Rene F., de T.M., Lutz-Bucher B., Gaiddon C., Loeffler J.P. Alteration of the Bcl-x/Bax ratio in a transgenic mouse model of amyotrophic lateral sclerosis: evidence for the implication of the p53 signaling pathway. Neurobiol. Dis. 7:2000;406-415.
55. Good P.F., Olanow C.W., Hsu A., Gordon J.W. Deprenyl, desmethyldeprenyl and ropinrole extend the life span of SOD-1 G86R transgenic mice. Neurosci. Abstr. 25:1999;342.20.
56. Götz J. Tau and transgenic animal models. Brain Res. Brain Res. Rev. 35:2001;266-286.
57. Graeber M.B., Moran L.B. Mechanisms of cell death in neurodegenerative diseases: fashion, fiction, and facts. Brain Pathol. 12:2002;385-390.
58. Graham S.H., Chen J. Programmed cell death in cerebral ischemia. J. Cereb. Blood Flow Metab. 21:2001;99-109.
59. Guglielmo M.A., Chan P.T., Cortez S., Stopa E.G., McMillan P., Johanson C.E., Epstein M., Doberstein C.E. The temporal profile and morphologic features of neuronal death in human stroke resemble those observed in experimental forebrain ischemia: the potential role of apoptosis. Neurol. Res. 20:1998;283-296.
60. Guo Q., Sebastian L., Sopher B.L., Miller M.W., Glazner G.W., Ware C.B., Martin G.M., Mattson M.P. Neurotrophic factors [activity-dependent neurotrophic factor (ADNF) and basic fibroblast growth factor (bFGF)] interrupt excitotoxic neurodegenerative cascades promoted by a PS1 mutation. PNAS. 96:1999;4125-4130.
61. Gurney M.E., Fleck T.J., Himes C.S., Hall E.D. Riluzole preserves motor function in a transgenic model of familial amyotrophic lateral sclerosis. Neurology. 50:1998;62-66.
62. Harper S.J., Saporito M.S., Hewson L., Young L., Smith D., Rigby M., Jackson P., Curtis N., Swain C., Hefti F., Vaught J.L., Sirinathsinghji D. CEP-1347 increases ChAT activity in culture and promotes cholinergic neurone survival following fimbria-fornix lesion. NeuroReport. 11:2000;2271-2276.
63. Härter L., Keel M., Hentze H., Leist M., Ertel W. Caspase-3 activity is present in cerebrospinal fluid from patients with traumatic brain injury. J. Neuroimmunol. 121:2001;76-78.
64. Hartmann A., Hirsch E.C. Parkinson's disease. The apoptosis hypothesis revisited. Adv. Neurol. 86:2001;143-153.
65. Hartmann A., Hunot S., Michel P.P., Vyas S., Faucheux B.A., Mouatt-Prigent A., Turmel H., Srinivasan A., Ruberg M., Evan G.I., Agid Y., Hirsch E.C. Caspase-3: a vulnerability factor and final effector in apoptotic death of dopaminergic neurons in Parkinson's disease. PNAS. 97:2000;2875-2880.
66. Hartmann A., Troadec J.D., Hunot S., Kikly K., Faucheux B.A., Mouatt-Prigent A., Ruberg M., Agid Y., Hirsch E.C. Caspase-8 is an effector in apoptotic death of dopaminergic neurons in Parkinson's disease, but pathway inhibition results in neuronal necrosis. J. Neurosci. 21:2001;2247-2255.
67. Hartmann A., Michel P.P., Troadec J.D., Mouatt-Prigent A., Faucheux B.A., Ruberg M., Agid Y., Hirsch E.C. Is Bax a mitochondrial mediator in apoptotic death of dopaminergic neurons in Parkinson's disease? J. Neurochem. 76:2001;1785-1793.
68. Hassouna I., Wickert H., Zimmermann M., Gillardon F. Increase in Bax expression in substantia nigra following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment of mice. Neurosci. Lett. 204:1996;85-88.
69. He B.P., Strong M.J. Motor neuronal death in sporadic amyotrophic lateral sclerosis (ALS) is not apoptotic. A comparative study of ALS and chronic aluminium chloride neurotoxicity in New Zealand white rabbits. Neuropathol. Appl. Neurobiol. 26:2000;150-160.
70. Heininger K. A unifying hypothesis of Alzheimer's disease: IV. Causation and sequence of events. Rev. Neurosci. 11:2000;213-328. (Spec. No.).
71. Heintz N., Zoghbi H.Y. Insights from mouse models into the molecular basis of neurodegeneration. Annu. Rev. Physiol. 62:2000;779-802.
72. Hensley K., Robinson K.A., Pye Q.N., Floyd R.A., Cheng I., Garland W.A., Irwin I. CPI-1189 inhibits interleukin 1beta-induced p38-mitogen-activated protein kinase phosphorylation: an explanation for its neuroprotective properties? Neurosci. Lett. 281:2000;179-182.
73. Hirsch E.C., Hunot S. Nitric oxide, glial cells and neuronal degeneration in parkinsonism. TIPS. 21:2000;163-165.
74. Hossmann K.A. Experimental models for the investigation of brain ischemia. Cardiovasc. Res. 39:1998;106-120.
75. Hossmann K.A. Neuronal apoptosis. A new means of treatment for cerebral ischemia? Anaesthesist. 50:2001;903-904.
76. Hunot S., Dugas N., Faucheux B., Hartmann A., Tardieu M., Debre P., Agid Y., Dugas B., Hirsch E.C. FcepsilonRII/CD23 is expressed in Parkinson's disease and induces, in vitro, production of nitric oxide and tumor necrosis factor-alpha in glial cells. J. Neurosci. 19:1999;3440-3447.
77. Hyman B.T., Van Horsen G.W., Damasio A.R., Barnes C.L. Alzheimer's disease: cell-specific pathology isolates the hippocampal formation. Science. 225:1984;1168-1170.
78. Jellinger K.A. Is there apoptosis in Lewy body disease? Acta Neuropathol. 97:1999;413-415.
79. Johnson S., Young-Chan C.S., Laping N.J., Finch C.E. Perforant path transection induces complement C9 deposition in hippocampus. Exp. Neurol. 138:1996;198-205.
80. Joseph J., Shukitt-Hale B., Denisova N.A., Martin A., Perry G., Smith M.A. Copernicus revisited: amyloid beta in Alzheimer's disease. Neurobiol. Aging. 22:2001;131-146.
81. Kaal E.C., Dijkstra S., Van Westerlaak M.G., Joosten E.A., Bär P.R. Experimental models for ALS - a short review. Neurosci. Res. Commun. 25:1999;1-11.
82. Kirkby D.L., Higgins G.A. Characterization of perforant path lesions in rodent models of memory and attention. Eur. J. Neurosci. 10:1998;823-838.
83. Komarov P.G., Komarova E.A., Kondratov R.V., Christov-Tselkov K., Coon J.S., Chernov M.V., Gudkov A.V. A chemical inhibitor of p53 that protects mice from the side effects of cancer therapy. Science. 285:1999;1733-1737.
84. Konitsiotis S., Saporito M.S., Flood D.G., Hyland K., Miller M., Lin Y.G., Arnold L.A., LePoole K., Bibbiani F., Blanchet P.J., Chase T.N. The neuroprotective effects of CEP-1347 in a primate model of MPTP-induced chronic progressive parkinsonism. Soc. Neurosci. Abstr. 25:1999;639.4.
85. Kostic V., Jackson-Lewis V., De Bilbao F., Dubois-Dauphin M., Przedborski S. Bcl-2: prolonging life in a transgenic model of familial amyotrophic lateral sclerosis. Science. 277:1997;559-562.
86. Kösel S., Egensperger R., Von Eitzen U., Mehraein P., Graeber M.B. On the question of apoptosis in the parkinsonian substantia nigra. Acta Neuropathol. 93:1997;105-108.
87. Kragten E., Lalande I., Zimmermann K., Roggo S., Schindler P., Müller D., van Oostrum J., Waldmeier P., Fürst P. Glyceraldehyde-3-phosphate dehydrogenase, the putative target of the antiapoptotic compounds CGP 3466 and R-(-)-deprenyl. J. Biol. Chem. 273:1998;5821-5828.
88. Kuntz C., Kinoshita Y., Beal M.F., Donehower L.A., Morrison R.S. Absence of p53: no effect in a transgenic mouse model of familial amyotrophic lateral sclerosis. Exp. Neurol. 165:2000;184-190.
89. Kurt M.A., Davies D.C., Kidd M., Duff K., Rolph S.C., Jennings K.H., Howlett D.R. Neurodegenerative changes associated with beta-amyloid deposition in the brains of mice carrying mutant amyloid precursor protein and mutant presenilin-1 transgenes. Exp. Neurol. 171:2001;59-71.
90. Langston J.W., Forno L.S., Tetrud J., Reeves A.G., Kaplan J.A., Karluk D. Evidence of active nerve cell degeneration in the substantia nigra of humans years after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine exposure. Ann. Neurol. 46:1999;598-605.
91. Laurer H.L., McIntosh T.K. Experimental models of brain trauma. Curr. Op. Neurol. 12:1999;715-721.
92. Le W.D., Jankovic J. Are dopamine receptor agonists neuroprotective in Parkinson's disease? Drugs Aging. 18:2001;389-396.
93. Lee M., Hyun D.H., Halliwell B., Jenner P. Effect of overexpression of wild-type and mutant Cu/Zn-superoxide dismutases on oxidative stress and cell death induced by hydrogen peroxide, 4-hydroxynonenal or serum deprivation: potentiation of injury by ALS-related mutant superoxide dismutases and protection by Bcl-2. J. Neurochem. 78:2001;209-220.
94. Lenzlinger P.M., Marx A., Trentz O., Kossmann T., Morganti-Kossmann M.C. Prolonged intrathecal release of soluble Fas following severe traumatic brain injury in humans. J. Neuroimmunol. 122:2002;167-174.
95. Li M., Ona V.O., Guegan C., Chen M., Jackson-Lewis V., Andrews L.J., Olszewski A.J., Stieg P.E., Lee J.P., Przedborski S., Friedlander R.M. Functional role of caspase-1 and caspase-3 in an ALS transgenic mouse model. Science. 288:2000;335-339.
96. Lipton P. Ischemic cell death in brain neurons. Physiol. Rev. 79:1999;1431-1568.
97. Liu X.Z., Xu X.M., Hu R., Du C., Zhang S.X., McDonald J.W., Dong H.X., Wu Y.J., Fan G.S., Jacquin M.F., Hsu C.Y., Choi D.W. Neuronal and glial apoptosis after traumatic spinal cord injury. J. Neurosci. 17:1997;5395-5406.
98. Love S., Barber R., Wilcock G.K. Apoptosis and expression of DNA repair proteins in ischaemic brain injury in man. NeuroReport. 9:1998;955-959.
99. Love S., Barber R., Srinivasan A., Wilcock G.K. Activation of caspase-3 in permanent and transient brain ischaemia in man. NeuroReport. 11:2000;2495-2499.
100. Love S., Barber R., Wilcock G.K. Neuronal death in brain infarcts in man. Neuropathol. Appl. Neurobiol. 26:2000;55-66.
101. MacManus J.P., Buchan A.M. Apoptosis after experimental stroke: fact or fashion? J. Neurotrauma. 17:2000;899-914.
102. Maeda K., Hata R., Gillardon F., Hossmann K.A. Aggravation of brain injury after transient focal ischemia in p53-deficient mice. Mol. Brain Res. 88:2001;54-61.
103. Maroney A.C., Glicksman M.A., Basma A.N., Walton K.M., Knight E. Jr., Murphy C.A., Bartlett B.A., Finn J.P., Angeles T., Matsuda Y., Neff N.T., Dionne C.A. Motoneuron apoptosis is blocked by CEP-1347 (KT 7515), a novel inhibitor of the JNK signaling pathway. J. Neurosci. 18:1998;104-111.
104. Maroney A.C., Finn J.P., Bozyczko-Coyne D., O'Kane T.M., Neff N.T., Tolkovsky A.M., Park D.S., Yan C.Y., Troy C.M., Greene L.A. CEP-1347 (KT7515), an inhibitor of JNK activation, rescues sympathetic neurons and neuronally differentiated PC12 cells from death evoked by three distinct insults. J. Neurochem. 73:1999;1912-2001.
105. Maroney A.C., Finn J.P., Connors T.J., Durkin J.T., Angeles T., Gessner G., Xu Z., Meyer S.L., Savage M.J., Greene L.A., Scott R.W., Vaught J.L. Cep-1347 (KT7515), a semisynthetic inhibitor of the mixed lineage kinase family. J. Biol. Chem. 276:2001;25302-25308.
106. Marshall K.A., Daniel S.E., Cairns N., Jenner P., Halliwell B. Upregulation of the anti-apoptotic protein Bcl-2 may be an early event in neurodegeneration: Studies on Parkinson's and incidental Lewy Body disease. Biochem. Biophys. Res. Commun. 240:1997;84-87.
107. Martin L.J. Neuronal death in amyotrophic lateral sclerosis is apoptosis: possible contribution of a programmed cell death mechanism. J. Neuropathol. Exp. Neurol. 58:1999;459-471.
108. Martin L.J. p53 is abnormally elevated and active in the CNS of patients with amyotrophic lateral sclerosis. Neurobiol. Dis. 7:2000;613-622.
109. Martin L.J. Neuronal cell death in nervous system development, disease, and injury. Int. J. Mol. Med. 7:2001;455-478.
110. Martinou J.-C., Dubois-Dauphin M., Stable J.K., Rodriguez I., Frankowski H., Missotten M., Albertini P., Talabot D., Catsica S., Pietra C., Huarte J. Overexpression of BCl-2 in transgenic mice protects neurons from naturally occurring death and experimental ischemia. Neuron. 13:1994;1017-1030.
111. Maruyama W., Akao Y., Youdim M.B., Davis B.A., Naoi M. Transfection-enforced Bcl-2 overexpression and an anti-Parkinson drug, rasagiline, prevent nuclear accumulation of glyceraldehyde-3-phosphate dehydrogenase induced by an endogenous dopaminergic neurotoxin, N-methyl-(R)-salsolinol. J. Neurochem. 78:2001;727-735.
112. Maruyama W., Youdim M.B., Naoi M. Antiapoptotic properties of rasagiline, N-propargylamine-1(R)-aminoindan, and its optical (S)-isomer, TV1022. Ann. N.Y. Acad. Sci. 939:2001;320-329.
113. Marx J. Neuroscience. New leads on the 'how' of Alzheimer's. Science. 293:2001;2192-2194.
114. Masliah E., Rockenstein E. Genetically altered transgenic models of Alzheimer's disease. J. Neural Transm. Suppl. 59:2000;175-183.
115. Masliah E., Sisk A., Mallory M., Mucke L., Schenk D., Games D. Comparison of neurodegenerative pathology in transgenic mice overexpressing V717F beta-amyloid precursor protein and Alzheimer's disease. J. Neurosci. 16:1996;5795-5811.
116. Mattson M.P. Apoptosis in neurodegenerative disorders. Nat. Rev. Mol. Cell Biol. 1:2000;120-129.
117. Mattson M.P., Duan W.Z. "Apoptotic" biochemical cascades in synaptic compartments: roles in adaptive plasticity and neurodegenerative disorders. J. Neurosci. Res. 58:1999;152-166.
118. Mattson M.P., Guo Q., Furukawa K., Pedersen W.A. Presenilins, the endoplasmic reticulum, and neuronal apoptosis in Alzheimer's disease. J. Neurochem. 70:1998;1-14.
119. Mattson M.P., Culmsee C., Yu Z.F. Apoptotic and antiapoptotic mechanisms in stroke. Cell Tissue Res. 301:2000;173-187.
120. McIntosh T.K., Saatman K.E., Raghupathi R., Graham D.I., Smith D.H., Lee V.M., Trojanowski J.Q. The Dorothy Russell Memorial Lecture. The molecular and cellular sequelae of experimental traumatic brain injury: pathogenetic mechanisms. Neuropathol. Appl. Neurobiol. 24:1998;251-267.
121. Migheli A., Cavalla P., Marino S., Schiffer D. A study of apoptosis in normal and pathologic nervous tissue after in situ end-labeling of DNA strand breaks. J. Neuropathol. Exp. Neurol. 53:1994;606-616.
122. Mochizuki H., Goto K., Mori H., Mizuno Y. Histochemical detection of apoptosis in Parkinson's disease. J. Neurol. Sci. 137:1996;120-123.
123. Moechars D., Lorent K., Van Leuven F. Premature death in transgenic mice that overexpress a mutant amyloid precursor protein is preceded by severe neurodegeneration and apoptosis. Neuroscience. 91:1999;819-830.
124. Mogi M., Harada M., Kondo T., Mizuno Y., Narabayashi H., Riederer P., Nagatsu T. bcl-2 protein is increased in the brain from parkinsonian patients. Neurosci. Lett. 215:1996;137-139.
125. Mu X.J., He J., Anderson D.W., Trojanowski J.Q., Springer J.E. Altered expression of bcl-2 and bax mRNA in amyotrophic lateral sclerosis spinal cord motor neurons. Ann. Neurol. 40:1996;379-386.
126. Muller W.E.G., Romero F.J., Perovic S., Pergande G., Pialoglou P. Protection of flupirtine on β-amyloid-induced apoptosis in neuronal cells in vitro: prevention of amyloid-induced glutathione depletion. J. Neurochem. 68:1997;2371-2377.
127. Nakagawa T., Zhu H., Morishima N., Li E., Xu J., Yankner B.A., Yuan J. Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta. Nature. 403:2000;98-103.
128. Ng I., Yeo T.T., Soong R., Tang W.T., Ong P.L., Lew T., Goh H.S., Smith D. Young Investigator's Award: induction of apoptosis following traumatic head injury in humans. Ann. Acad. Med. Singapore. 28:1999;363-365.
129. Ng I., Yeo T.T., Tang W.Y., Soong R., Ng P.Y., Smith D.R. Apoptosis occurs after cerebral contusions in humans. Neurosurgery. 46:2000;949-956.
130. Offen D., Beart P.M., Cheung N.S., Pascoe C.J., Hochman A., Gorodin S., Melamed E., Bernard R., Bernard O. Transgenic mice expressing human Bcl-2 in their neurons are resistant to 6-hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity. PNAS. 95:1998;5789-5794.
131. Osborne N.N., Cazevieille C., Pergande G., Wood J.P. Induction of apoptosis in cultured human retinal pigment epithelial cells is counteracted by flupirtine. Invest. Ophthalmol. Visual Sci. 38:1997;1390-1400.
132. Osborne N.N., Cazevieille C., Wood J.P., Nash M.S., Pergande G., Block F., Kosinski C., Schwarz M. Flupirtine, a nonopioid centrally acting analgesic, acts as an NMDA antagonist. Gen. Pharmacol. 30:1998;255-263.
133. Padosch S.A., Vogel P., Bottiger B.W. Neuronal apoptosis following cerebral ischemia. Basis, physiopathology and treatment strategies. Anaesthesist. 50:2001;905-920.
134. Pasinelli P., Borchelt D.R., Houseweart M.K., Cleveland D.W., Brown R.H. Jr. Caspase-1 is activated in neural cells and tissue with amyotrophic lateral sclerosis-associated mutations in copper-zinc superoxide dismutase. PNAS. 95:1998;15763-15768.
135. Paterson I.A., Fennig C.J., Gelowitz D.L., Waldmeier P., Boulton A.A. CGP3466 prevents neuronal death in models of ischaemia and seizure in vivo. J. Neurochem. 70(Suppl. 1):1998;S6C.
136. Paterson I.A., Waldmeier P., Boulton A.A. CGP 3466 and CGP 3466B prevent cytosine arabinoside-induced apoptosis in cultures of cerebellar neurones. J. Neurochem. 70(Suppl. 1):1998;S11B.
137. Paterson I.A., Zhang D., Warrington R.C., Boulton A.A. R-deprenyl and R-2-heptyl-N-methylpropargylamine prevent apoptosis in cerebellar granule neurons induced by cytosine arabinoside but not low extracellular potassium. J. Neurochem. 70:1998;515-523.
138. Pedersen W.A., Luo H., Kruman I., Kasarskis E., Mattson M.P. The prostate apoptosis response-4 protein participates in motor neuron degeneration in amyotrophic lateral sclerosis. FASEB J. 14:2000;913-924.
139. Perovic S., Schleger C., Pergande G., Iskric S., Ushijima H., Rytik P., Müller W.E.G. The triaminopyridine flupirtine prevents cell death in rat cortical cells induced by N-methyl-D-aspartate and gp120 of HIV-1. Eur. J. Pharmacol. Mol. Pharmacol. 288:1994;27-33.
140. Perovic S., Pialoglou P., Schroder H.C., Pergande G., Muller W.E. Flupirtine increases the levels of glutathione and Bc1-2 in hNT (human Ntera/D1) neurons: mode of action of the drug-mediated anti-apoptotic effect. Eur. J. Pharmacol. 317:1996;157-164.
141. Perovic S., Schroder H.C., Pergande G., Ushijima H., Muller W.E. Effect of flupirtine on Bcl-2 and glutathione level in neuronal cells treated in vitro with the prion protein fragment (PrP106-126). Exp. Neurol. 147:1997;518-524.
142. Perry G., Nunomura A., Smith M.A. A suicide note from Alzheimer disease neurons? Nat. Med. 4:1998;897-898.
143. Peterson D.A., Lucidi-Phillipi C.A., Eagle K.L., Gage F.H. Perforant path damage results in progressive neuronal death and somal atrophy in layer II of entorhinal cortex and functional impairment with increasing postdamage age. J. Neurosci. 14:1994;6872-6885.
144. Petroske E., Meredith G.E., Callen S., Totterdell S., Lau Y.S. Mouse model of parkinsonism: a comparison between subacute MPTP and chronic MPTP/probenecid treatment. Neuroscience. 106:2001;589-601.
145. Prudlo J., Koenig J., Gräser J., Burckhardt E., Mestres P., Menger M., Roemer K. Motor neuron cell death in a mouse model of FALS is not mediated by the p53 cell survival regulator. Brain Res. 879:2000;183-187.
146. Pulliam L., Irwin I., Kusdra L., Rempel H., Flitter W.D., Garland W.A. CPI-1189 attenuates effects of suspected neurotoxins associated with AIDS dementia: a possible role for ERK activation. Brain Res. 893:2001;95-103.
147. Qiu J., Whalen M.J., Lowenstein P., Fiskum G., Fahy B., Darwish R., Aarabi B., Yuan J., Moskowitz M.A. Upregulation of the Fas receptor death-inducing signaling complex after traumatic brain injury in mice and humans. J. Neurosci. 22:2002;3504-3511.
148. Rabey J.M., Sagi I., Huberman M., Melamed E., Korczyn A., Giladi N., Inzelberg R., Djaldetti R., Klein C., Berecz G. Rasagiline mesylate, a new MAO-B inhibitor for the treatment of Parkinson's disease: a double-blind study as adjunctive therapy to levodopa. Clin. Neuropharmacol. 23:2000;324-330.
149. Raghupathi R., Graham D.I., McIntosh T.K. Apoptosis after traumatic brain injury. J. Neurotrauma. 17:2000;927-938.
150. Raina A.K., Hochman A., Zhu X.W., Rottkamp C.A., Nunomura A., Siedlak S.L., Boux H., Castellani R.J., Perry G., Smith M.A. Abortive apoptosis in Alzheimer's disease. Acta Neuropathol. 101:2001;305-310.
151. Reed J.C. Apoptosis-based therapies. Nat. Rev. Drug Discov. 1:2002;111-121.
152. Rink A., Fung K.M., Trojanowski J.Q., Lee V.M.Y., Neugebauer E., McIntosh T.K. Evidence of apoptotic cell death after experimental traumatic brain injury in the rat. Am. J. Pathol. 147:1995;1575-1583.
153. Rohn T.T., Head E., Su J.H., Anderson A.J., Bahr B.A., Cotman C.W., Cribbs D.H. Correlation between caspase activation and neurofibrillary tangle formation in Alzheimer's disease. Am. J. Pathol. 158:2001;189-198.
154. 2+ concentration. Eur. J. Pharmacol. 294:1995;469-473.
155. Sagot Y., Toni N., Perrelet D., Lurot S., King B., Rixner H., Mattenberger L., Waldmeier P.C., Kato A.C. An orally active anti-apoptotic molecule (CGP 3466B) preserves mitochondria and enhances survival in an animal model of motoneuron disease. Br. J. Pharmacol. 131:2000;721-728.
156. Sahuquillo J., Poca M.A., Amoros S. Current aspects of pathophysiology and cell dysfunction after severe head injury. Curr. Pharmaceut. Design. 7:2001;1475-1503.
157. Saille C., Marin P., Martinou J.C., Nicole A., London J., Ceballos-Picot I. Transgenic murine cortical neurons expressing human Bcl-2 exhibit increased resistance to amyloid beta-peptide neurotoxicity. Neuroscience. 92:1999;1455-1463.
158. Saito N., Yamamoto T., Watanabe T., Abe Y., Kumagai T. Implications of p53 protein expression in experimental spinal cord injury. J. Neurotrauma. 17:2000;173-182.
159. Saporito M.S., Brown E.R., Carswell S., DiCamillo A.M., Miller M.S., Murakata C., Neff N.T., Vaught J.L., Haun F.A. Preservation of cholinergic activity and prevention of neuron death by CEP-1347/KT-7515 following excitotoxic injury of the nucleus basalis magnocellularis. Neuroscience. 86:1998;461-472.
160. Saporito M.S., Brown E.M., Miller M.S., Carswell S. CEP-1347/KT-7515, an inhibitor of c-jun N-terminal kinase activation, attenuates the 1-methyl-4-phenyl tetrahydropyridine-mediated loss of nigrostriatal dopaminergic neurons In vivo. J. Pharmacol. Exp. Ther. 288:1999;421-427.
161. Sathasivam S., Ince P.G., Shaw P.J. Apoptosis in amyotrophic lateral sclerosis: a review of the evidence. Neuropathol. Appl. Neurobiol. 27:2001;257-274.
162. Schlüter T., Struy H., Schönfeld P. Protection of mitochondrial integrity from oxidative stress by the triaminopyridine derivative flupirtine. FEBS Lett. 481:2000;42-46.
163. Schmidt W.J., Schuster G., Wacker E., Pergande G. Antiparkinsonian and other motor effects of flupirtine alone and in combination with dopaminergic drugs. Eur. J. Pharmacol. 327:1997;1-9.
164. Schulz J.B., Weller M., Moskowitz M.A. Caspases as treatment targets in stroke and neurodegenerative diseases. Ann. Neurol. 45:1999;421-429.
165. Sekhon L.H., Fehlings M.G. Epidemiology, demographics, and pathophysiology of acute spinal cord injury. Spine. 26:2001;S2-S12.
166. Shaw P.J. Calcium, glutamate, and amyotrophic lateral sclerosis: more evidence but no certainties. Ann. Neurol. 46:1999;803-805.
167. Sperandio S., de B.I., Bredesen D.E. An alternative, nonapoptotic form of programmed cell death. PNAS. 97:2000;14376-14381.
168. Spooren W.P., Hengerer B. DNA laddering and caspase 3-like activity in the spinal cord of a mouse model of familial amyotrophic lateral sclerosis. Cell. Mol. Biol. 46:2000;63-69.
169. Spooren W.P.J.M., Gentsch C., Wiessner C. Tunel-positive cells in the substantia nigra of C57BL/6 mice after a single bolus of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Neuroscience. 85:1998;649-651.
170. Springer J.E., Nottingham S.A., McEwen M.L., Azbill R.D., Jin Y. Caspase-3 apoptotic signaling following injury to the central nervous system. Clin. Chem. Lab. Med. 39:2001;299-307.
171. Stadelmann C., Deckwerth T.L., Srinivasan A., Bancher C., Bruck W., Jellinger K., Lassmann H. Activation of caspase-3 in single neurons and autophagic granules of granulovacuolar degeneration in Alzheimer's disease. Evidence for apoptotic cell death. Am. J. Pathol. 155:1999;1459-1466.
172. Tarkowski E., Rosengren L., Blomstrand C., Jensen C., Ekholm S., Tarkowski A. Intrathecal expression of proteins regulating apoptosis in acute stroke. Stroke. 30:1999;321-327.
173. Tatton N.A. Increased caspase 3 and Bax immunoreactivity accompany nuclear GAPDH translocation and neuronal apoptosis in Parkinson's disease. Exp. Neurol. 166:2000;29-43.
174. Tatton W.G., Chalmers-Redman R.M.E. Modulation of gene expression rather than monoamine oxidase inhibition: (-)-deprenyl-related compounds in controlling neurodegeneration. Neurology. 47(Suppl. 3):1996;S171-S183.
175. Tatton N.A., Kish S.J. In situ detection of apoptotic nuclei in the substantia nigra compacta of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice using terminal deoxynucleotidyl transferase labelling and acridine orange staining. Neuroscience. 77:1997;1037-1048.
176. Tatton N.A., Maclean-Fraser A., Tatton W.G., Perl D.P., Olanow C.W. A fluorescent double-labeling method to detect and confirm apoptotic nuclei in Parkinson's disease. Ann. Neurol. 44(Suppl. 1):1998;S142-S148.
177. Tatton W.G., Chalmers-Redman R.M., Elstner M., Leesch W., Jagodzinski F.B., Stupak D.P., Sugrue M.M., Tatton N.A. Glyceraldehyde-3-phosphate dehydrogenase in neurodegeneration and apoptosis signaling. J. Neural Transm., Suppl. 2000;77-100.
178. Tatton W.G., Chalmers-Redman R.M., Sud A., Podos S.M., Mittag T.W. Maintaining mitochondrial membrane impermeability. an opportunity for new therapy in glaucoma? Surv. Ophthalmol. 45(Suppl. 3):2001;S277-S283.
179. Tatton W.G., Chalmers-Redman R.M., Ju W.J., Mammen M., Carlile G.W., Pong A.W., Tatton N.A. Propargylamines induce antiapoptotic new protein synthesis in serum- and nerve growth factor (NGF)-withdrawn, NGF-differentiated PC-12 cells. J. Pharmacol. Exp. Ther. 301:2002;753-764.
180. Trimmer P.A., Smith T.S., Jung A.B., Bennett J.P. Jr. Dopamine neurons from transgenic mice with a knockout of the p53 gene resist MPTP neurotoxicity. Neurodegeneration. 5:1996;233-239.
181. Troost D., Aten J., Morsink F., De Jong J.M.B.V. Apoptosis in amyotrophic lateral sclerosis is not restricted to motor neurons. Bcl-2 expression is increased in unaffected post-central gyrus. Neuropathol. Appl. Neurobiol. 21:1995;498-504.
182. Troy C.M., Rabacchi S.A., Friedman W.J., Frappier T.F., Brown K., Shelanski M.L. Caspase-2 mediates neuronal cell death induced by β-amyloid. J. Neurosci. 20:2000;1386-1392.
183. Troy C.M., Rabacchi S.A., Xu Z., Maroney A.C., Connors T.J., Shelanski M.L., Greene L.A. beta-Amyloid-induced neuronal apoptosis requires c-Jun N-terminal kinase activation. J. Neurochem. 77:2001;157-164.
184. Turmel H., Hartmann A., Parain K., Douhou A., Srinivasan A., Agid Y., Hirsch E.C. Caspase-3 activation in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. Movement Disord. 16:2001;185-189.
185. Van Leuven F. Single and multiple transgenic mice as models for Alzheimer's disease. Progr. Neurobiol. 61:2000;305-312.
186. Vila M., Jackson-Lewis V., Vukosavic S., Djaldetti R., Liberatore G., Offen D., Korsmeyer S.J., Przedborski S. Bax ablation prevents dopaminergic neurodegeneration in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease. PNAS. 98:2001;2837-2842.
187. Vukosavic S., Dubois-Dauphin M., Romero N., Przedborski S. Bax and Bcl-2 interaction in a transgenic mouse model of familial amyotrophic lateral sclerosis. J. Neurochem. 73:1999;2460-2468.
188. Vukosavic S., Stefanis L., Jackson-Lewis V., Guégan C., Romero N., Chen C.P., Dubois-Dauphin M., Przedborski S. Delaying caspase activation by Bcl-2: a clue to disease retardation in a transgenic mouse model of amyotrophic lateral sclerosis. J. Neurosci. 20:2000;9119-9125.
189. Vyas S., Javoy-Agid F., Herrero M.T., Strada O., Boissiere F., Hibner U., Agid Y. Expression of bcl-2 in adult human brain regions with special reference to neurodegenerative disorders. J. Neurochem. 69:1997;223-231.
190. Waldmeier P.C., Boulton A.A., Cools A.R., Kato A.C., Tatton W.G. Neurorescuing effects of the GAPDH ligand CGP 3466B. J. Neural Transm. Suppl. 60:2000;197-214.
191. Waldmeier P.C., Spooren W.P., Hengerer B. CGP 3466 protects dopaminergic neurons in lesion models of Parkinson's disease. Naunyn-Schmiedeberg's Arch. Pharmacol. 362:2000;526-537.
192. Walters T.L., Irwin I., Delfani K., Langston J.W., Janson A.M. Diethyldithiocarbamate causes nigral cell loss and dopamine depletion with nontoxic doses of MPTP. Exp. Neurol. 156:1999;62-70.
193. L but not Bcl-2 genes reduced lesion size after permanent middle cerebral artery occlusion in mice. Neurosci. Lett. 268:1999;119-122.
194. Williams S., Raghupathi R., MacKinnon M.A., McIntosh T.K., Saatman K.E., Graham D.I. In situ DNA fragmentation occurs in white matter up to 12 months after head injury in man. Acta Neuropathol. 102:2001;581-590.
195. Wüllner U., Kornhuber J., Weller M., Schulz J.B., Löschmann P.A., Riederer P., Klockgether T. Cell death and apoptosis regulating proteins in Parkinson's disease a cautionary note. Acta Neuropathol. 97:1999;408-412.
196. Xiang Z., Ho L., Valdellon J., Borchelt D., Kelley K., Spielman L., Aisen P.S., Pasinetti G.M. Cyclooxygenase (COX)-2 and cell cycle activity in a transgenic mouse model of Alzheimer's disease neuropathology. Neurobiol. Aging. 23:2002;327-334.
197. Yakovlev A.G., Knoblach S.M., Fan L., Fox G.B., Goodnight R., Faden A.I. Activation of CPP32-like caspases contributes to neuronal apoptosis and neurological dysfunction after traumatic brain injury. J. Neurosci. 17:1997;7415-7424.
198. Yang L., Matthews R.T., Schulz J.B., Klockgether T., Liao A.W., Martinou J.-C., Penney J.B., Hyman B.T., Beal M.F. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity is attenuated in mice overexpressing Bcl-2. J. Neurosci. 18:1998;8145-8152.
199. Y and nick-end labeling are positive in spinal motor neurons in amyotrophic lateral sclerosis. Acta Neuropathol. 88:1994;207-211.
200. Youdim M.B., Wadia A., Tatton W., Weinstock M. The anti-Parkinson drug rasagiline and its cholinesterase inhibitor derivatives exert neuroprotection unrelated to MAO inhibition in cell culture and in vivo. Ann. N.Y. Acad. Sci. 939:2001;450-458.
201. Zhang D., Berry M.D., Paterson I.A., Boulton A.A. Loss of mitochondrial membrane potential is dependent on the apoptotic program activated: prevention by R-2HMP. J. Neurosci. Res. 58:1999;284-292.
202. Zhang X., Chen J., Graham S.H., Du L., Kochanek P.M., Draviam R., Guo F., Nathaniel P.D., Szabo C., Watkins S.C., Clark R.S. Intranuclear localization of apoptosis-inducing factor (AIF) and large scale DNA fragmentation after traumatic brain injury in rats and in neuronal cultures exposed to peroxynitrite. J. Neurochem. 82:2002;181-191.
203. Zimmermann K.C., Bonzon C., Green D.R. The machinery of programmed cell death. Pharmacol. Ther. 92:2001;57-70.