Mechanisms of neuronal death in disease: defining the models and the players.
Dysregulation of life and death at the cellular level leads to a variety of diseases. In the nervous system, aberrant neuronal death is an outstanding feature of neurodegenerative diseases. Since the discovery of the caspase family of proteases, much effort has been made to determine how caspases function in disease, including neurodegenerative diseases. Although many papers have been published examining caspases in neuronal death and disease, the pathways have not been fully clarified. In the present review, we examine the potential players in the death pathways, the current tools for examining these players and the models for studying neurological disease. Alzheimer's disease, the most common neurodegenerative disorder, and cerebral ischaemia, the most common cause of neurological death, are used to illustrate our current understanding of death signalling in neurodegenerative diseases. A better understanding of the neuronal death pathways would provide targets for the development of therapeutic interventions for these diseases.
Ribe
Elena M
EM
Department of Pathology, Taub Center for the Study of Alzheimer's Disease and the Aging Brain, Columbia University College of Physicians and Surgeons, 630 W. 168th Street, New York, NY 10032, USA.
Serrano-Saiz
Esther
E
Akpan
Nsikan
N
Troy
Carol M
CM
D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D020169:Caspases / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D009422:Nervous System Diseases / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D015398:Signal Transduction
D020169:Caspases
Neuron. 2005 Mar 3;45(5):639-42
15748837
Biochem Biophys Res Commun. 2000 Nov 2;277(3):655-9
11062009
Mol Cell Neurosci. 2001 Dec;18(6):702-14
11749044
Nat Med. 1998 Oct;4(10):1177-81
9771752
Exp Neurol. 1999 Mar;156(1):130-7
10192784
Mol Neurobiol. 1995 Feb;10(1):19-45
7598831
Am J Pathol. 1999 Nov;155(5):1459-66
10550301
J Biol Chem. 2001 Jan 5;276(1):529-34
11013246
Curr Opin Neurobiol. 1996 Oct;6(5):667-72
8937832
Science. 1997 Feb 21;275(5303):1132-6
9027315
Lancet. 1998 Oct;352 Suppl 3:SIII1-4
9803954
J Neurosci. 2008 Mar 19;28(12):3051-9
18354008
Nature. 1992 Apr 30;356(6372):768-74
1574116
Annu Rev Neurosci. 1990;13:171-82
1970230
J Neurochem. 1984 Nov;43(5):1369-74
6149259
Stroke. 1995 Apr;26(4):636-42; discussion 643
7709411
Int J Mol Med. 1998 May;1(5):797-9
9852298
Proc Natl Acad Sci U S A. 1998 May 26;95(11):6448-53
9600986
Nature. 1991 Feb 21;349(6311):704-6
1671712
Brain Res Mol Brain Res. 2001 Apr 18;89(1-2):133-46
11311984
Methods. 1999 Jun;18(2):117-26
10356342
Brain Res Mol Brain Res. 2001 Dec 16;97(1):103-13
11744168
Am J Hum Genet. 2006 Jun;78(6):936-46
16685645
J Neurosci. 1997 Jun 1;17(11):4180-9
9151735
Neurology. 2000 Nov 14;55(9):1249-55
11092223
J Neurosci. 2001 Aug 1;21(15):5528-34
11466424
Cell Death Differ. 2004 Nov;11(11):1234-41
15297885
Mol Biol Cell. 2006 May;17(5):2150-7
16495337
EMBO J. 1995 Apr 3;14(7):1304-13
7729409
Nat Cell Biol. 2006 Jan;8(1):72-7
16362053
J Biol Chem. 1999 Aug 13;274(33):23426-36
10438520
Proc Natl Acad Sci U S A. 2003 Aug 19;100(17):10032-7
12888622
J Biol Chem. 2002 Jan 4;277(1):432-8
11606597
J Biol Chem. 2008 Feb 29;283(9):5402-13
18086677
J Biol Chem. 2002 Nov 1;277(44):42074-81
12200426
Brain Res Bull. 1998 Jul 1;46(4):281-309
9671259
Proc Natl Acad Sci U S A. 1986 Jun;83(11):3929-33
3459164
Stroke. 2004 Feb;35(2):572-7
14726551
J Pharmacol Exp Ther. 1987 Nov;243(2):784-91
2890761
N Engl J Med. 2006 Feb 9;354(6):553-5
16467542
J Biol Chem. 2007 Sep 7;282(36):26202-9
17613533
Nat Cell Biol. 2001 Feb;3(2):128-33
11175744
Cell. 1999 Apr 30;97(3):395-406
10319819
Science. 2000 Dec 22;290(5500):2303-4
11125143
J Cereb Blood Flow Metab. 1998 Aug;18(8):868-75
9701347
Brain Res Brain Res Protoc. 1999 Jul;4(2):173-84
10446412
Proc Natl Acad Sci U S A. 2008 Mar 18;105(11):4133-8
18332441
Brain Behav Immun. 2003 Jun;17(3):152-7
12706413
Cell. 1993 Nov 19;75(4):641-52
8242740
Hum Mol Genet. 2001 Aug 1;10(16):1665-71
11487570
Science. 1983 Apr 29;220(4596):536-7
6836300
J Biol Chem. 1997 Apr 11;272(15):9677-82
9092497
Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1550-5
9037091
Mol Cell. 2003 Feb;11(2):529-41
12620239
J Biol Chem. 1999 Aug 20;274(34):24007-13
10446169
Cell. 1993 Nov 19;75(4):653-60
8242741
J Med Genet. 2000 Oct;37(10):766-70
11015454
Am J Pathol. 2001 Mar;158(3):1173-7
11238065
Cell. 2000 Jul 7;102(1):43-53
10929712
J Neurosci. 1996 Jan;16(1):253-61
8613791
Oncogene. 2007 Feb 26;26(9):1324-37
17322918
Mol Cell. 2008 Apr 25;30(2):123-35
18439892
Neurobiol Dis. 2005 Oct;20(1):27-37
16137564
Cell. 2000 Jul 7;102(1):33-42
10929711
J Biol Chem. 1999 Jul 23;274(30):21011-6
10409650
Brain Pathol. 2005 Jan;15(1):84-7
15779241
Toxicol Lett. 2003 Apr 4;139(2-3):153-62
12628750
Stroke. 2007 Nov;38(11):3000-6
17916764
Neurobiol Dis. 2007 Jan;25(1):179-88
17067805
Science. 1993 Aug 13;261(5123):921-3
8346443
Am J Pathol. 1999 Jan;154(1):255-70
9916940
Neuron. 1995 Nov;15(5):1203-18
7576662
J Cereb Blood Flow Metab. 1996 Mar;16(2):186-94
8594049
Hum Mutat. 2006 Sep;27(9):888-96
16917905
EMBO J. 2007 Jan 10;26(1):197-208
17159900
J Neurosci. 2000 Feb 15;20(4):1386-92
10662829
JAMA. 1997 Oct 22-29;278(16):1363-71
9343469
J Neurosci. 1998 Jun 15;18(12):4439-50
9614221
Stroke. 1993 Dec;24(12):2002-8; discussion 2008-9
8248983
J Neural Transm (Vienna). 2000;107(2):203-31
10847561
Neuroradiology. 2007 Feb;49(2):93-102
17177065
Amino Acids. 2008 Jan;34(1):169-74
17297564
Nature. 1998 Apr 9;392(6676):560
9560151
Cell. 2008 May 16;133(4):693-703
18485876
J Cereb Blood Flow Metab. 2001 Apr;21(4):321-33
11323518
J Biol Chem. 1997 Jul 18;272(29):17907-11
9218414
Science. 2001 Aug 24;293(5534):1491-5
11520988
J Neurosci. 1998 May 15;18(10):3659-68
9570797
Ann Neurol. 1992 Oct;32(4):555-63
1456740
Nature. 2006 Mar 16;440(7082):352-7
16541076
Prog Neuropsychopharmacol Biol Psychiatry. 2003 Apr;27(2):267-82
12657366
J Neurosci Methods. 1999 Jul 1;89(1):25-31
10476680
Behav Brain Res. 2008 Aug 22;191(2):246-55
18485495
Neuron. 1995 Feb;14(2):447-56
7857652
Brain Pathol. 1991 Apr;1(3):213-6
1669710
Biochem Soc Symp. 2003;(70):233-42
14587296
Nature. 2004 May 6;429(6987):75-9
15129283
Acta Neuropathol. 2000 May;99(5):469-81
10805089
Biochemistry. 2007 Apr 10;46(14):4398-407
17371051
Mol Neurodegener. 2006 Jul 03;1:5
16930452
Cerebrovasc Dis. 2006;21 Suppl 2:9-20
16651810
Cell Death Differ. 2008 Feb;15(2):322-31
17975551
Semin Neurol. 2006 Nov;26(5):499-506
17048151
J Neurochem. 2006 Jul;98(1):258-66
16805812
J Neurosci. 2001 Sep 15;21(18):7127-34
11549723
Trends Pharmacol Sci. 2003 Aug;24(8):402-8
12915049
Neuroscience. 1995 Oct;68(3):615-9
8577361
Nat Med. 2000 Apr;6(4):397-404
10742146
Stroke. 2004 Jun;35(6):1443-8
15118177
Life Sci. 1987 May 25;40(21):2059-66
3586851
Neurosci Res. 2000 Jun;37(2):113-25
10867174
Traffic. 2002 Nov;3(11):763-70
12383342
J Neurosci. 2004 Nov 10;24(45):10040-6
15537872
Nat Rev Mol Cell Biol. 2001 Aug;2(8):589-98
11483992
Arch Neurol. 2003 Mar;60(3):369-76
12633148
J Clin Invest. 2004 Jul;114(1):121-30
15232619
J Neurosci. 2005 Feb 2;25(5):1149-58
15689551
J Exp Med. 1997 Mar 3;185(5):933-40
9120399
Neurobiol Dis. 2001 Dec;8(6):1036-45
11741399
Folia Neuropathol. 2004;42(4):235-7
15679042
Oncogene. 2008 Jan 10;27(3):387-96
17637755
Ann N Y Acad Sci. 2000;924:184-93
11193796
Science. 1997 Feb 21;275(5303):1129-32
9027314
Physiol Rev. 2001 Apr;81(2):741-66
11274343
Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13896-901
12368474
Neuroscience. 2001;104(2):299-310
11377835
Cell. 1995 Feb 10;80(3):401-11
7859282
Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):15318-23
11742085
J Neurochem. 2005 Jan;92(2):294-301
15663477
Mol Cell Neurosci. 1997;9(3):159-69
9245499
Am J Pathol. 1999 Dec;155(6):2153-65
10595944
Nature. 1997 Jul 3;388(6637):31
9214497
Lancet. 2006 Jul 29;368(9533):387-403
16876668
J Neurosci. 1999 Jun 15;19(12):5026-33
10366635
Science. 1996 Oct 4;274(5284):99-102
8810256
Curr Drug Targets CNS Neurol Disord. 2005 Aug;4(4):435-52
16101559
Brain Res. 2002 Jan 11;924(2):133-40
11750898
Nature. 1997 Jul 10;388(6638):190-5
9217161
J Neuropathol Exp Neurol. 2003 Apr;62(4):329-39
12722825
J Neurosci. 2008 Jan 23;28(4):788-97
18216187
J Neurosci. 2007 Jan 24;27(4):893-900
17251431
Nature. 1994 Nov 3;372(6501):92-4
7969426
Acta Neuropathol. 2008 Jan;115(1):5-38
18038275
EMBO J. 2003 Aug 15;22(16):4132-42
12912912
J Neurochem. 2003 May;85(4):1026-36
12716434
Nature. 2000 Jan 6;403(6765):98-103
10638761
J Mol Neurosci. 2005;27(2):167-74
16186627
J Cell Biol. 1994 Jan;124(1-2):1-6
8294493
J Cell Biol. 2004 May 10;165(3):347-56
15123740
Nat Rev Neurosci. 2003 May;4(5):399-415
12728267
Neurology. 1992 Mar;42(3 Pt 1):631-9
1549228
J Neurosci. 1993 Aug;13(8):3510-24
8101871
Br J Cancer. 1972 Aug;26(4):239-57
4561027
Nat Rev Mol Cell Biol. 2000 Nov;1(2):120-9
11253364
J Cereb Blood Flow Metab. 1998 Feb;18(2):180-5
9469161
Folia Neuropathol. 2004;42(1):9-14
15119739
Cell Death Differ. 2001 Sep;8(9):921-32
11526447
Neurosci Lett. 1988 Jul 8;89(3):323-7
3419631
Neuroreport. 2000 Aug 3;11(11):2495-9
10943710
J Neurosci. 2000 Apr 15;20(8):2817-24
10751433
Science. 1984 Nov 16;226(4676):850-2
6093256
Biochem J. 2007 Jul 1;405(1):11-9
17437405
Neurobiol Dis. 2005 Dec;20(3):814-22
16125396
Stroke. 1995 Sep;26(9):1670-4; discussion 1675
7544927
J Neurosci. 1999 Jul 15;19(14):5932-41
10407032
Prog Biophys Mol Biol. 2008 May;97(1):60-78
18076975
Science. 2004 May 7;304(5672):843-6
15073321
J Biol Chem. 2006 Feb 10;281(6):3254-60
16339151
Biochemistry. 2000 Sep 5;39(35):10831-9
10978169
Biochem Soc Trans. 2002 Aug;30(4):552-7
12196135
J Biol Chem. 1998 Jan 30;273(5):2926-30
9446604
J Cell Biol. 2000 May 1;149(3):613-22
10791975
Brain Res. 2000 Feb 21;856(1-2):93-100
10677615
Biochem Biophys Res Commun. 2002 May 3;293(2):722-6
12054529
Brain Res. 2000 Jun 9;867(1-2):62-9
10837798
EMBO Rep. 2006 Oct;7(10):988-94
17016456
Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):15188-93
12415117
Ann Neurol. 1981 Aug;10(2):184-92
7283403
Nature. 1995 Jun 29;375(6534):754-60
7596406
J Cereb Blood Flow Metab. 2003 Sep;23(9):1010-9
12973017
Neurology. 1992 Sep;42(9):1681-8
1307688
J Neurosci. 2002 Jan 1;22(1):133-41
11756496
J Neurochem. 2005 Nov;95(3):834-47
16135089
Science. 1995 Aug 18;269(5226):970-3
7638621
Neuron. 2003 Jul 31;39(3):409-21
12895417
ILAR J. 2003;44(2):85-95
12652003
Acta Biochim Pol. 2004;51(1):245-52
15094846
Nat Genet. 2000 Aug;25(4):402-5
10932182
Nature. 1995 Feb 9;373(6514):523-7
7845465
Proc Natl Acad Sci U S A. 2005 Oct 4;102(40):14314-20
16183742
Neurobiol Aging. 2000 Nov-Dec;21(6):843
11124428
J Biol Chem. 1999 Oct 22;274(43):30764-9
10521466
Mol Cell Neurosci. 2003 Jun;23(2):302-13
12812761
Proc Natl Acad Sci U S A. 1999 May 11;96(10):5752-7
10318956
Physiol Rev. 1999 Oct;79(4):1431-568
10508238
Cereb Cortex. 1991 Jan-Feb;1(1):103-16
1822725
Nat Rev Mol Cell Biol. 2007 May;8(5):405-13
17377525
Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):13287-92
9371838
Nat Rev Immunol. 2005 Aug;5(8):629-40
16034365
J Hirnforsch. 1991;32(3):277-82
1779131
J Neurosci. 2004 Mar 17;24(11):2750-9
15028768