Apoptosis in neurodegenerative disorders

Current Opinion in Neurology

Volumn 10, Issue 4, 1997, Pages 299-305

  Stefanis, Leonidas ^a,b   Burke, Robert E ^a   Greene, Lloyd A ^a  

^a Columbia University ^*  (United States)

^b NEUROLOGICAL INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANIMAL MODEL; APOPTOSIS; DEGENERATIVE DISEASE; HUMAN; NONHUMAN; PATHOLOGY; REVIEW; TISSUE CULTURE;

EID: 0030759613     PISSN: 13507540     EISSN: None     Source Type: Journal    
DOI: 10.1097/00019052-199708000-00004     Document Type: Review

References (78)

1. Bredesen DE: Neural apoptosis. Ann Neurol 1995, 8:839-851.
2. Kerr JFR, Wyllie AH, Currie AR: Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 1972, 26:239-257.
3. Oppenheim RW: Cell death during development of the nervous system. Annu Rev Neurosci 1991, 14:453-501.
4. Clarke PGH: Developmental cell death: morphological diversity and multiple mechanisms. Anat Embryol 1990, 181:195-213.
5. Kerr JFR, Gobe GC, Winterford CM, Harmon BV: Anatomical methods in cell death. In: Methods in cell biology: cell death. Edited by Schwartz LM, Osborne BA. New York: Academic Press; 1995:1-27.
6. Gavrieli Y, Sherman Y, Ben-Sasson SA: Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol 1992, 119:493-501.
7. Hengartner MO, Horvitz HR: C. elegans cell survival gene ced-9 encodes a functional homolog of the mammalian proto-oncogene bcl-2. Cell 1994, 76:665-676.
8. Yuan J, Shaham S, Ledoux S, Ellis HM, Horvitz HR: The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1β-converting enzyme. Cell 1993, 75:641-652.
9. Davies AM: The bcl-2 family of proteins, and the regulation of neuronal survival. Trends Neurosci 1995, 18:355-358.
10. Fraser A, Evan G: A licence to kill. Cell 1996, 85:781-784.
11. Shaham S, Horvitz HR: Developing Caenorhabditls elegans neurons may contain both cell-death protective and killer activities. Gen Dev 1996, 10:578-591.
12. Zhao B, Chrest FJ, Horton WE, Sisodia SS, Kusiak JW: Expression of mutant amyloid precursor proteins induces apoptosis in PC12 cells. J Neurosci Res 1997, 47:253-263.
13. •].
14. Yamatsuji T, Matsui T, Okamoto T, Komatsuzaki K, Takeda S, Fukumoto H, Iwatsubo T, Suzuki N, Asami-Okada A, Ireland S, et al.: G protein-mediated neuronal DNA fragmentation induced by familial Alzheimer's disease-associated mutants of APP. Science 1996, 272:1349-1352. Important papers, linking APP mutations to apoptosis, irrespective of their amyloidogenic potential; apoptotic effects appear to be mediated through interaction with Go proteins.
15. Deng G, Pike CJ, Cotman CW: Alzheimer-associated presenilin-2 confers increased sensitivity to apoptosis in PC12 cells. FEBS Lett 1996, 397:50-54.
16. •].
17. •].
18. •] demonstrate that PS2 mutations are associated with cell-autonomous apoptotic effects in neuronal cells, and that PS2 may actually be part of certain apoptotic pathways.
19. Kusiak JW, Izzo JA, Zhao B: Neurodegeneration in Alzheimer disease. Is apoptosis involved? Molecular and Chemical Neuropathology 1996, 28:153-162. A balanced review of cell culture and animal models of Alzheimer's disease, and of neuropathological evidence of apoptosis in this disorder.
20. Mattson MP, Cheng B, Davis D, Bryant K, Lieberburg I, Rydel RE: β-amyloid peptides destabilize calcium homeostasis and render human cortical neurons vulnerable to excitotoxicity. J Neurosci 1992, 12:376-389.
21. Paradis E, Douillard H, Koutroumanis M, Goodyer C, LeBlanc A: Amyloid β peptide of Alzheimer's disease downregulates bcl-2 and upregulates bax expression in human neurons. J Neurosci 1996, 16:7533-7539. Increased ratio of bax to bcl-2 induced by Aβ 1-42 does not in and of itself cause apoptosis, but potentiates apoptosis induced by oxidative stress in human fetal cortical neurons.
22. Ikeda H, Yamaguchi M, Sugai S, Aze Y, Narumiya S, Kakizuka A: Expanded polyglutamine in the Machado-Joseph disease protein induces cell death in vitro and in vivo. Nature Gen 1996, 13:196-202. Proapoptotic function of a truncated form of the MJD gene, possibly through formation of insoluble aggregates, in non-neuronal cells. Whether this correlates with in vivo effects in neuronal cells remains to be seen.
23. Goldberg YP, Nicholson DW, Rasper DM, Kalchman MA, Koide HB, Graham RK, Bromm M, Kazemi-Esfarjani P, Thornberry NA, Vaillancourt JP, Hayden MR: Cleavage of huntingtin by apopain, a proapoptotic cysteine protease, is modulated by the polyglutamine tract. Nature Gen 1996, 13:442-449. Association of huntingtin proteolysis by a caspase with apoptosis, but the results need to be controlled for the length of the construct used and to be confirmed with the full length protein.
24. Zeitlin S, Liu J-P, Chapman DL, Papaioannou VE, Efstratiadis A: Increased apoptosis and early embryonic lethality in mice nullizygous for the Huntington's disease gene homologue. Nature Gen 1995, 11:155-163.
25. LeFevre S, Burglen L, Reboullet S, Clermont O, Burlet P, Viollet L, Benichou B, Cruaud C, Millassea P, Zeviani M, et al.: Identification and characterization of a spinal muscular atrophy- determining gene. Cell 1995, 80:155-165.
26. Roy N, Mahadevan MS, McLean M, Shutler G, Yaraghi Z, Farahani R, Baird S, Besner-Johnston A, Lefebvre C, Kang X, et al.: The gene for neuronal apoptosis inhibitory protein is partially deleted in individuals with spinal muscular atrophy. Cell 1995, 80:167-178.
27. Brahe C, Bertini E: Spinal Muscular Atrophies: recent insight and impact on molecular diagnosis. J Mol Med 1996, 74:555-562.
28. Uren AG, Pakusch M, Hawkins CJ, Puls KL, Vaux DL: Cloning and expression of apoptosis inhibitory protein homologs that function to inhibit apoptosis and/or bind tumor necrosis factor-associated factors. Proc Natl Acad Sci U S A 1996, 93:4974-4978.
29. Liston P, Roy N, Tamal K, Lefebvre C, Baird S, Cherton- Horvat G, Farahani R, McLean M, Ikeda J-E, MacKenzie A, Korneluk RG: Suppression of apoptosis in mammalian cells by NAIP and a related family of IAP genes. Nature 1996, 379:349-353.
30. Rabizadeh Shahrooz, Gralla EB, Borchelt DR, Gwinn R, Valentine JS, Sisodia S, Wong P, Lee M, Hahn H, Bredesen DE: Mutations associated with amyotrophic lateral sclerosis convert superoxide dismutase from an antiapoptotic gene to a proapoptotic gene: studies in yeast and neural cells. Proc Natl Acad Sci U S A 1995, 92:3024-3028.
31. Games D, Adams D, Alessandrini R, Barbour R, Berthelette P, Blackwell C, Carr T, Clemes J, Donaldson T, Gillespie F, et al.: Alzheimer-type neuropathology in transgenic mice overexpressing V717 b-amyloid precursor protein. Nature 1995, 373:523-527.
32. Masliah E, Sisk A, Mallory M, Mucke L, Schenk D, Games D: Comparison of neurodegenerative pathology in transgenic mice overexpressing V717 β-amyloid precursor protein and Alzheimer's disease. J Neurosci 1996, 16:5795-5811. Very detailed ultrastructural studies show classic apoptotic morphology of neuronal cells in these transgenics. However, there is no comparison with non-transgenic controls. The relative paucity of neuronal cell loss in this model in the face of evidence of apoptotic cell death is puzzling.
33. LaFerla FM, Tinkle BT, Bieberich CJ, Haudenschild CC, Jay G: The Alzheimer's A β-peptide induces neurodegeneration and apoptotic cell death in transgenic mice. Nature Gen 1995, 9:21-29.
34. Wood KA, Youle RJ: The role of free radicals and p53 in neuron apoptosis in vivo. J Neurosci 1995, 15:5851-5857.
35. LaFerla FM, Hall CK, Ngo L, Jay G: Extracellular deposition of β-amyloid upon p53-dependent neuronal cell death in transgenic mice. J Clin Invest 1996, 98:1626-1632. Interesting correlative evidence for a p53-mediated apoptotic pathway in transgenics overexpressing intracellular Aβ peptide. Cross-breeding studies with p53 null mice may be more revealing.
36. Jackson-Lewis V, Jakowek M, Burke RE, Przedborski S: Time-course and morphology of dopaminergic neuronal death caused by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Neurodegeneration 1995, 4:257-269.
37. Tatton NA, Kish SJ: 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 1997, 4:1037-1048. Using TUNEL and a new in situ acridine orange staining technique, the authors clearly show that apoptosis occurs in SN cells in this relatively protracted form of MPTP administration.
38. Trimmer PA, Smith ST, Jung AB, Bennett JP: Dopamine neurons from transgenic mice with a knockout of the p53 gene resist MPTP neurotoxicity. Neurodegeneration 1996, 5:233-239. Intriguing report that suggests p53 may be necessary for MPTP-induced apoptosis of SN neurons; unclear whether there is abrogation or delay of death in p53-/-mice.
39. 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 1996, 204:85-88.
40. Cleveland DW, Bruijn LI, Wong ,PC, Marszalek JR, Vechio JD, Lee MK, Xu X-S, Borchelt DR, Sisodia SS, Price DL: Mechanisms of selective motor neuron death in transgenic mouse models of motor neuron disease. Neurology 1996, 47:S54-S62.
41. Hirano A: Neuropathology of ALS: An overview. Neurology 1996, 47:S63-S66.
42. Pumarola M, Anor S, Majo N, Borras D, Ferrer I: Spinal Muscular Atrophy in Holstein-Friesian calves. Acta Neuropath 1997, 93:178-183.
43. Coulpier M, Junier M-P, Peschanski M, Dreyfus PA: Bcl-2 sensitivity differentiates two pathways for motoneuronal death in the wobbler mutant mouse. J Neurosci 1996, 16:5897-5904. A clear dissociation of the effects of bcl-2 on 'pathological' and developmental or axotomy-induced cell death. More studies of this type need to be done, especially in the transgenic ALS models.
44. Migheli A, Attanasio A, Lee W-H, Bayer SA, Ghetti B: Detection of apoptosis in weaver cerebellum by electron microscopic in situ end-labeling of fragmented DNA. Neurosci Lett 1995, 199:53-56.
45. Wullner U, Loschmann P-A, Weller M, Klockgether T: Apoptotic cell death in the cerebellum of mutant weaver and lurcher mice. Neurosci Lett 1995, 200:109-112.
46. Oo TF, Blazeski R, Harrison SMW, Henchcliffe C, Mason CA, Roffler-Tarlov SK, Burke RE: Neuron death in the substantia nigra of weaver mouse occurs late in development and is not apoptotic. J Neurosci 1996, 16:6134-6145. Using silver, thionin, and TUNEL staining, in addition to electron microscopy, the authors demonstrate a nonapoptotic form of cell death in SN of weaver mice. Ultrastructural features are unique, not conforming to either necrosis or classic apoptotic morphology.
47. Smale G, Nichols NR, Brady DR, Finch CE, Horton WE Jr: Evidence for apoptotic cell death in Alzheimer's disease. Exp Neurol 1995, 133:225-230.
48. Lassman H, Bancher C, Breitschopf H, Wegiel J, Bobinski M, Jellinger K, Wisniewski MM: Cell death in Alzheimer's disease evaluated by DNA fragmentation in situ. Acta Neuropath 1995, 89:35-41.
49. Lassman H: Patterns of synaptic and nerve cell pathology in Alzheimer's disease. Behav Brain Res 1996, 78:9-14.
50. Dragunow M, Faull RLM, Lawlor P, Beilharz EJ, Singleton K, Walker EB, Mee E: In situ evidence for DNA fragmentation in Huntington's disease striatum and Alzheimer's disease temporal lobes. Neuroreport 1995, 6:1053-1057.
51. Ferrer I, Tortosa A, Macaya A, Sierra A, Moreno D, Munnel F, Blanco R, Squier W: Evidence of DNA fragmentation following hypoxia ischemia in the infant rat brain, and transient forebrain ischemia in the adult gebril. Brain Path 1994, 4:115-122.
52. Anderson AJ, Su JH, Cotman CW: DNA damage and apoptosis in Alzheimer's disease: colocalizatlon with c-jun immunoreactivity, relationship to brain area, and effect of postmortem delay. J Neurosci 1996, 16:1710-1718. Many interesting points: prolonged postmortem delay (more than 6. 5 h) increases background TUNEL staining; c-Jun immunoreactivity is increased in Alzheimer's disease and colocalizes with TUNEL staining (despite the authors' claim, TUNEL positive neurons do not have the classic apoptotic morphology); general regional correlation of TUNEL staining with Alzheimer's disease pathology. The large numbers of TUNEL positive and c-Jun positive neurons are puzzling.
53. Troncoso JC, Sukhov RR, Kawas CH, Koliatsos VE: In situ labeling of dying cortical neurons in normal aging and in Alzheimer's disease: correlations with senile plaques and disease progression. J Neuropath Exper Neurol 1996, 55:1134-1142. Neocortical layer III and CA1 and CA4 hippocampal areas show TUNEL staining in early Alzheimer's disease and in 'presymptomatic' cases; morphology not classically apoptotic.
54. Satou T, Cummings BJ, Cotman CW: Immunoreactivity for bcl-2 protein within neurons in the Alzheimer's disease brain increases with disease severity. Brain Res 1995, 697:35-43.
55. Su JH, Satou T, Anderson AJ, Cotman CW: Up-regulation of bcl-2 is associated with neuronal DNA damage in Alzheimer's disease. Neuroreport 1996, 7:437-440.
56. Su JH, Deng G, Cotman CW: Bax protein expression is increased in Alzheimer's brain: correlations with DNA damage, bcl-2 expression, and brain pathology. J Neuropath Exper Neurol 1997, 56:86-93. Association of Bax, but not Bcl-2, immunoreactivity with early neurofilament hyperphosphorylation indicates that bax may be related to neurodegeneration in Alzheimer's disease.
57. O'Barr S, Shultz J, Rogers J: Expression of the protooncogene bcl-2 in Alzheimer's disease brain. Neurobiol Aging 1996, 17:131-136.
58. Drache B, Diehl GE, Beyreuther K, Perlmutter LS, Koning G: Bcl-xl-specific antibody labels activated microglia associated with Alzheimer's disease and other pathological states. J Neurosci Res 1996, 47:98-108.
59. Ham J, Babij C, Whitfeld J, Pfarr CM, Lallemand D, Yaniv M, Rubin LL: A c-Jun dominant negative mutant protects sympathetic neurons against programmed cell death. Neuron 1995, 14:927-939.
60. Estus S, Zaks WJ, Freeman RS, Gruda M, Bravo R, Johnson EM Jr: Altered gene expression in neurons during programmed cell death: identification of c-jun as necessary for neuronal apoptosis. J Cell Biol 1994, 127:1717-1727.
61. Herzog KH, Morgan JI: Cellular immediate-early genes and cell death in the nervous system. Neuropath Appl Neurobiol 1996, 22:484-488.
62. Park DS, Farinelli SE, Greene LA: Inhibitors of cyclin-dependent kinases promote survival of post-mitotic neuronally differentiated PC12 cells and sympathetic neurons. J Biol Chem 1996, 271:1-9.
63. Nagy Z, Esiri MM, Smith AD: Expression of cell division markers in the hippocampus in Alzheimer's disease and other neurodegenerative conditions. Acta Neuropath 1997, 93:294-300.
64. Arendt T, Rodel L, Gartner U, Holzer M: Expression of the cyclin-dependent kinase inhibitor p16 in Alzheimer's disease. Neuroreport 1996, 7:3047-3049. Intriguing results, that suggest activation of cell cycle components in degenerating neurons in Alzheimer's disease; however, p16 has been shown to be protective in various models of apoptosis.
65. Kitamura Y, Shimohama S, Kamoshima W, Matsuoka Y, Nomura Y, Taniguchi T: Changes of p53 in the brains of patients with Alzheimer's disease. Biochem Biophys Res Com 1997, 232:418-421.
66. Mochizuki H, Goto K, Mori H, Mizuno Y: Histochemical detection of apoptosis in Parkinson's disease. J Neurol Sci 1996, 137:120-123.
67. Kosel S, Egensperger H, von Eitzen U, Mehraein P, Graeber MB: On the question of apoptosis in the parkinsonian substantisa nigra. Acta Neuropath 1997, 93:105-108.
68. Anglade P, Vyas S, Javoy-Agid F, Herrero MT, Michel PP, Marquez J, Mouatt-Prigert A, Ruberg M, Hirsch EC, Agid Y: Apoptosis and autophagy in nigral neurons of patients with PD. Histol Histochem 1997, 12:25-31.
69. Tompkins MM, Basgall EJ, Zamrini E, Hill WD: Apoptotic-like changes in Lewy-body-associated disorders and normal aging in substantia nigra neurons. Am J Pathol 1997, 150:119-131. The first clear demonstration of a pigmented cell in the SN undergoing apoptosis in a case with diffuse Lewy body disease, using fluoroscein/propridium iodide staining. The electron microscopy pictures shown are less convincing.
70. 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 1996, 215:137-139.
71. y and nick-end labeling are positive in spinal motor neurons in amyotrophic lateral sclerosis. Acta Neuropath 1994, 88:207-211.
72. Troost D, Aten J, Morsink F, de Jong JMBV: Apoptosis in amyotrophic lateral sclerosis is not restricted to motor neurons. Bcl-2 expression is increased in unaffected post-central gyrus. Neuropath Appl Neurobiol 1995, 21:498-504.
73. Mu X, He J, Anderson DW, Trojanowski JQ, Springer JE: Altered expression of bcl-2 and bax mRNA in amyotrophic lateral sclerosis spinal cord motor neurons. Ann Neurol 1996, 40:379-386. Upregulation of bax and downregulation of bcl-2 are clearly demonstrated in lumbar spinal motor neurons in ALS.
74. Gagliardini V, Fernandez P-A, Lee RKK, Drexler HCA, Rotello RJ, Fishman MC, Yuan J: Prevention of vertebrate neuronal death by the crmA gene. Science 1994, 263:824-828.
75. Troy CM, Stefanis L, Prochiantz A, Greene LA, Shelanski ML: The contrasting roles of ICE- family proteases and interleukin 1-β in apoptosis induced by trophic factor withdrawal and by copper/zinc superoxide dismutase down-regulation. Proc Natl Acad Sci U S A 1996, 93:5635-5640. It is shown that caspases are necessary for neuronal apoptosis induced by oxidative stress or withdrawal of trophic support, but that the specific members of the caspase family that are required may be different in each paradigm.
76. Schwartz LM, Miligan CE: Cold thoughts of death: the role of ICE proteases in neuronal cell death. Trends Neurosci 1996, 19:552-562. A review of the role of caspases in neuronal cell death.
77. •].
78. Hara H, Friedlander RM, Gagliardini V, Ayata C, Fink K, Huang Z, Shimizu-Sasamata M, Yuan J, Moskowitz MA: Inhibition of interleukin [1b] converting enzyme family proteases reduces ischemic and excitotoxic neuronal damage. Proc Natl Acad Sci U S A 1997, 94:2007-2012. Two important papers that demonstrate that inhibition of caspases may substantially improve neurological outcome and reduce the extent of injury in animal stroke models.