Mitochondrial and Cell Death Mechanisms in Neurodegenerative Diseases.
Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS) are the most common human adult-onset neurodegenerative diseases. They are characterized by prominent age-related neurodegeneration in selectively vulnerable neural systems. Some forms of AD, PD, and ALS are inherited, and genes causing these diseases have been identified. Nevertheless, the mechanisms of the neuronal cell death are unresolved. Morphological, biochemical, genetic, as well as cell and animal model studies reveal that mitochondria could have roles in this neurodegeneration. The functions and properties of mitochondria might render subsets of selectively vulnerable neurons intrinsically susceptible to cellular aging and stress and overlying genetic variations, triggering neurodegeneration according to a cell death matrix theory. In AD, alterations in enzymes involved in oxidative phosphorylation, oxidative damage, and mitochondrial binding of Aβ and amyloid precursor protein have been reported. In PD, mutations in putative mitochondrial proteins have been identified and mitochondrial DNA mutations have been found in neurons in the substantia nigra. In ALS, changes occur in mitochondrial respiratory chain enzymes and mitochondrial cell death proteins. Transgenic mouse models of human neurodegenerative disease are beginning to reveal possible principles governing the biology of selective neuronal vulnerability that implicate mitochondria and the mitochondrial permeability transition pore. This review summarizes how mitochondrial pathobiology might contribute to neuronal death in AD, PD, and ALS and could serve as a target for drug therapy.
Department of Pathology, Division of Neuropathology and Department of Neuroscience, Johns Hopkins University School of Medicine, 558 Ross Building, 720 Rutland Avenue, Baltimore, Maryland 21205-2196, USA; martinl@jhmi.edu ; Tel.: +410-502-5170;
Lee J
LJ
Martin
Science. 1997 Jun 27;276(5321):2045-7
9197268
Mol Pathol. 1998 Dec;51(6):293-304
10193509
J Cell Biol. 1997 Oct 6;139(1):205-17
9314540
Nature. 1998 Oct 1;395(6701):451-2
9774100
J Neurosci. 1997 Sep 15;17(18):7053-9
9278541
J Neurosurg. 2004 Jul;101(1):128-37
15255263
Biochem Biophys Res Commun. 2003 May 9;304(3):487-97
12729583
Am J Alzheimers Dis Other Demen. 2009 Apr-May;24(2):95-121
19116299
J Neuropathol Exp Neurol. 1999 May;58(5):459-71
10331434
Nat Neurosci. 2002 Nov;5 Suppl:1039-42
12403981
Science. 1997 Oct 24;278(5338):687-9
9381178
Dev Biol. 1966 Feb;13(1):77-94
5923195
J Cell Biol. 1998 Dec 14;143(6):1691-703
9852160
BMC Neurosci. 2003 Jul 15;4:16
12864925
Cell Biol Int. 2007 Sep;31(9):893-9
17485229
Neuron. 2004 Jul 8;43(1):19-30
15233914
Cell. 1996 Nov 15;87(4):619-28
8929531
Cell. 1997 Nov 28;91(5):627-37
9393856
N Engl J Med. 1992 May 28;326(22):1464-8
1349424
J Biol Chem. 1969 Nov 25;244(22):6049-55
5389100
Drugs Aging. 2001;18(9):685-716
11599635
Ann Neurol. 1991 Oct;30(4):572-80
1789684
Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):8968-73
12084935
Am J Pathol. 1999 Nov;155(5):1459-66
10550301
J Neurosci. 1992 Feb;12(2):376-89
1346802
Brain Res. 1999 Dec 4;849(1-2):67-77
10592288
Eur J Neurosci. 2002 Jul;16(1):44-54
12153530
Proc Natl Acad Sci U S A. 2000 Feb 29;97(5):2286-90
10681452
Biochem J. 2001 Sep 1;358(Pt 2):349-58
11513733
Nature. 1991 Oct 31;353(6347):844-6
1944558
Science. 1997 Feb 21;275(5303):1132-6
9027315
Mol Cell Neurosci. 2002 May;20(1):21-9
12056837
J Exp Biol. 2003 Jun;206(Pt 12):1993-2000
12756281
J Biol Chem. 1995 Jun 9;270(23):13998-4006
7539795
J Neuropathol Exp Neurol. 1971 Jan;30(1):75-90
5542543
J Cell Physiol. 2000 Jan;182(1):41-9
10567915
Acta Neuropathol. 1999 Apr;97(4):408-12
10208281
Neuroscience. 1996 Oct;74(3):675-83
8884764
Acta Neuropathol. 2004 May;107(5):461-74
15029445
J Comp Neurol. 2007 Jan 1;500(1):20-46
17099894
J Neurosci. 2006 Jan 4;26(1):41-50
16399671
Curr Opin Cell Biol. 2002 Oct;14(5):653-60
12231362
J Biol Chem. 2002 Sep 13;277(37):34295-302
12097334
J Virol. 1998 Nov;72(11):8586-96
9765397
Toxicology. 2005 Nov 5;215(1-2):1-24
16054742
Science. 2003 Jan 10;299(5604):256-9
12446870
J Cell Biol. 2003 Apr 14;161(1):41-54
12695498
J Neurochem. 2002 Apr;81(1):170-7
12067230
Nat Cell Biol. 2004 Sep;6(9):849-60
15300255
Nature. 1991 Feb 21;349(6311):704-6
1671712
Dement Geriatr Cogn Disord. 2003;16(4):212-9
14512716
J Neurosci. 2006 Aug 30;26(35):9057-68
16943564
Science. 2003 Oct 31;302(5646):841
14593171
Science. 1999 Apr 9;284(5412):339-43
10195903
Cell. 2005 Nov 4;123(3):383-96
16269331
Science. 2001 Apr 27;292(5517):727-30
11326099
Cancer Cell. 2002 Sep;2(3):183-92
12242151
Curr Opin Cell Biol. 2002 Dec;14(6):727-33
12473346
Cell Biol Int. 2000;24(4):253-60
10816327
Ann Neurol. 2007 Dec;62(6):553-9
18074357
Comp Biochem Physiol B Biochem Mol Biol. 2008 Sep;151(1):10-27
18602321
Neuron. 2003 Oct 9;40(2):401-13
14556717
Acta Neuropathol. 1991;82(4):239-59
1759558
Biochemistry. 2009 Mar 10;48(9):2045-52
19152501
Science. 2002 Oct 25;298(5594):789-91
12399581
J Biol Chem. 1992 Jul 25;267(21):14592-7
1378836
Trends Pharmacol Sci. 2002 Jan;23(1):19-24
11804647
J Neurosci. 2007 Jul 11;27(28):7469-75
17626207
Ann Neurol. 2006 Apr;59(4):714-9
16532471
Biochem J. 1998 Dec 1;336 ( Pt 2):287-90
9820802
Int Rev Cytol. 1980;68:251-306
7014501
Nutr Rev. 1989 Jan;47(1):23-5
2649802
Ann Neurol. 1998 Sep;44(3 Suppl 1):S142-8
9749586
Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7162-6
7638161
J Neurochem. 2008 Dec;107(5):1271-83
18808448
Biochim Biophys Acta. 2009 Jan;1792(1):3-13
19022377
Nat Med. 2008 Oct;14(10):1097-105
18806802
J Neurochem. 1998 Nov;71(5):2041-8
9798929
J Pharmacol Exp Ther. 2007 Aug;322(2):709-20
17496168
J Biol Chem. 2000 Jun 16;275(24):18344-9
10747881
Curr Med Chem. 2003 Aug;10(16):1527-33
12871124
J Cereb Blood Flow Metab. 2002 Aug;22(8):935-50
12172379
Exp Neurol. 2002 May;175(1):35-48
12009758
J Bioenerg Biomembr. 1998 Jun;30(3):277-84
9733094
J Biol Chem. 1999 Aug 13;274(33):23426-36
10438520
Neuroscience. 2003;117(3):567-75
12617963
J Neurosci. 2001 Oct 1;21(19):7551-60
11567045
J Comp Neurol. 1997 Jun 2;382(2):247-59
9183692
Neurosci Lett. 1999 Jun 11;268(1):29-32
10400070
Cell. 1996 Jul 12;86(1):147-57
8689682
Am J Pathol. 1998 Aug;153(2):447-56
9708805
Neurosci Lett. 2004 Sep 9;367(3):273-7
15337248
J Biol Chem. 2002 Jan 4;277(1):432-8
11606597
Biochem Pharmacol. 1994 Aug 17;48(4):675-81
8080440
J Cell Biochem. 2001;81(3):393-400
11255222
Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4386-91
9539746
Ann Neurol. 2006 Mar;59(3):570-4
16358336
Science. 1997 Jul 18;277(5324):370-2
9219694
Oncogene. 2001 Jul 27;20(33):4457-65
11494141
J Biol Chem. 2005 May 13;280(19):19051-61
15757910
J Biol Chem. 1999 Jul 16;274(29):20049-52
10400609
Pharmacol Res. 2005 Jan;51(1):1-17
15519530
Mol Genet Metab. 2002 Feb;75(2):97-107
11855928
J Neurochem. 2007 Dec;103(5):2066-76
17868326
Cell. 1995 Jan 13;80(1):167-78
7813013
Brain Res Bull. 1998 Jul 1;46(4):281-309
9671259
Am J Pathol. 1994 Dec;145(6):1358-81
7992840
Int J Mol Med. 2001 May;7(5):455-78
11295106
J Clin Invest. 1996 Oct 1;98(7):1626-32
8833912
Science. 2000 Dec 1;290(5497):1717-21
11099404
Neurosci Lett. 2000 Sep 8;291(1):44-8
10962150
Neuron. 2002 Aug 29;35(5):921-33
12372286
Nat Genet. 1998 Feb;18(2):106-8
9462735
J Biol Chem. 2008 Mar 28;283(13):8446-52
18171673
Ann Neurol. 2006 Aug;60(2):197-203
16802290
Proc Natl Acad Sci U S A. 1998 Oct 27;95(22):12896-901
9789011
Cell. 1997 Nov 14;91(4):479-89
9390557
Curr Opin Cell Biol. 2005 Aug;17(4):384-8
15975781
Nature. 1996 Jan 25;379(6563):349-53
8552191
Cell Death Differ. 2005 Feb;12(2):162-76
15592434
Cell. 1999 Apr 30;97(3):395-406
10319819
Nat Neurosci. 2008 Mar;11(3):301-8
18297066
J Neurochem. 1997 Nov;69(5):2064-74
9349552
Nature. 2005 Feb 17;433(7027):696-8
15716937
FEBS Lett. 2009 Jan 22;583(2):449-55
19116152
Biochem J. 1999 Jul 15;341 ( Pt 2):233-49
10393078
J Neurobiol. 2002 Feb 15;50(3):181-97
11810634
Proc Natl Acad Sci U S A. 2009 Feb 10;106(6):2007-11
19174508
Am J Pathol. 2009 Feb;174(2):574-85
19116365
Oncogene. 2001 Jul 19;20(32):4305-16
11466611
Nat Struct Biol. 2002 Jun;9(6):442-6
11967568
J Comp Neurol. 2001 May 7;433(3):299-311
11298357
J Neurochem. 2003 Apr;85(1):234-47
12641745
J Biol Chem. 1999 Aug 20;274(34):24007-13
10446169
Trends Mol Med. 2008 Feb;14(2):45-53
18218341
Biochim Biophys Acta. 2004 Jul 9;1657(2-3):105-14
15238267
Cell. 2000 Jul 7;102(1):43-53
10929712
J Biol Chem. 2002 Aug 16;277(33):29803-9
12065594
Science. 1994 Jun 17;264(5166):1772-5
8209258
Am J Pathol. 2000 Aug;157(2):401-10
10934145
Hum Mutat. 2008 Jun;29(6):832-40
18401856
Proc Natl Acad Sci U S A. 1994 Aug 16;91(17):8292-6
8058797
J Bioenerg Biomembr. 2005 Jun;37(3):129-42
16167170
Science. 2002 Jul 19;297(5580):353-6
12130773
Science. 1989 Nov 3;246(4930):670-3
2530630
J Cell Biol. 1970 May;45(2):221-34
5513605
Neuropathol Appl Neurobiol. 2007 Apr;33(2):204-11
17359361
J Neurochem. 2001 Jan;76(1):295-301
11146002
Ann N Y Acad Sci. 2003 Jun;991:93-100
12846977
Nature. 2002 Sep 26;419(6905):367-74
12353028
Nat Genet. 2008 May;40(5):572-4
18372902
Neurobiol Dis. 2000 Jun;7(3):169-91
10860783
Neuron. 2004 Nov 18;44(4):595-600
15541308
J Neurosci. 2000 Nov 1;20(21):7994-8004
11050120
J Neuropathol Exp Neurol. 1997 Aug;56(8):887-900
9258259
J Neurosci. 2000 Aug 15;20(16):6021-9
10934251
Neuron. 2005 Feb 17;45(4):489-96
15721235
J Neurosci. 1999 Apr 15;19(8):2996-3006
10191317
Neuroscience. 2007 Nov 23;149(4):822-33
17961929
Exp Cell Res. 2003 Feb 1;283(1):1-16
12565815
Science. 1982 Mar 5;215(4537):1237-9
7058341
Brain Res. 2006 Feb 23;1075(1):1-12
16460709
J Neurotrauma. 2002 Jul;19(7):815-28
12184852
Prog Neurobiol. 2006 Dec;80(5):241-68
17188795
J Neurochem. 1998 Jul;71(1):281-7
9648876
J Neurochem. 2000 Jan;74(1):134-42
10617114
Apoptosis. 2007 May;12(5):841-55
17453156
Cell. 2000 Jul 7;102(1):33-42
10929711
Nature. 2000 Oct 12;407(6805):777-83
11048728
Acta Neuropathol. 2001 Oct;102(4):293-305
11603803
Nature. 2005 Mar 31;434(7033):658-62
15800627
Am J Epidemiol. 2003 Jun 1;157(11):1015-22
12777365
Neuroscience. 1997 Mar;77(2):393-401
9472399
J Physiol. 2004 Feb 15;555(Pt 1):45-59
14660707
Eur J Neurosci. 1995 Jul 1;7(7):1627-40
7551189
Brain Res. 2004 Oct 1;1022(1-2):54-61
15353213
Pharmacol Ther. 1997 Sep;75(3):153-77
9504137
Annu Rev Genet. 2005;39:359-407
16285865
J Neurosci. 1996 Dec 1;16(23):7533-9
8922409
N Engl J Med. 2001 May 31;344(22):1688-700
11386269
Ann N Y Acad Sci. 1999;893:33-41
10672228
Sci Am. 1993 Apr;268(4):46-52
8446881
Science. 1993 Aug 20;261(5124):1047-51
8351519
J Neuropathol Exp Neurol. 1997 Aug;56(8):933-44
9258263
Biochem Biophys Res Commun. 1998 Aug 28;249(3):754-8
9731209
Hum Mol Genet. 2005 Nov 15;14(22):3477-92
16207731
Ann Neurol. 1995 Jul;38(1):73-84
7611729
Cell. 1997 Oct 17;91(2):231-41
9346240
Neurobiol Aging. 2003 Mar-Apr;24(2):197-211
12498954
J Comp Neurol. 2004 Jul 5;474(4):524-34
15174070
Cell Prolif. 1991 Mar;24(2):203-14
2009322
J Mass Spectrom. 2007 Dec;42(12):1583-9
18085547
Nat Rev Neurosci. 2001 Jul;2(7):492-501
11433374
Curr Opin Neurobiol. 1998 Jun;8(3):398-404
9687353
Brain Res. 1994 May 9;645(1-2):253-64
8062088
Nat Genet. 2006 Oct;38(10):1184-91
16964263
J Neurol Sci. 2009 Jan 15;276(1-2):170-4
19000626
Science. 1998 Nov 13;282(5392):1318-21
9812896
J Neuropathol Exp Neurol. 2006 Dec;65(12):1103-10
17146283
J Cell Biol. 2002 Apr 29;157(3):455-68
11980920
Free Radic Biol Med. 2003 Feb 15;34(4):397-408
12566065
Lancet. 2003 Mar 15;361(9361):888-9
12648963
Free Radic Biol Med. 2008 Aug 1;45(3):284-94
18466779
Science. 2000 Feb 18;287(5456):1265-9
10678833
Proc Natl Acad Sci U S A. 2005 Aug 23;102(34):12005-10
16103352
Proc Natl Acad Sci U S A. 1996 Jun 11;93(12):5709-14
8650157
Proc Natl Acad Sci U S A. 2004 Jun 15;101(24):9103-8
15181200
J Biol Chem. 2004 Apr 30;279(18):18614-22
14985362
J Exp Med. 1997 Apr 21;185(8):1481-6
9126928
Annu Rev Neurosci. 2003;26:267-98
12704221
Curr Biol. 1999 May 20;9(10):543-6
10339431
Lab Invest. 1965 Apr;14:343-71
14279874
J Comp Neurol. 2001 Apr 23;433(1):4-22
11283945
J Biol Chem. 1999 Apr 23;274(17):11549-56
10206961
J Biol Chem. 2001 Jan 19;276(3):1954-60
11044447
Mol Cell Neurosci. 2003 Oct;24(2):419-29
14572463
J Neurosci. 2005 Jul 6;25(27):6449-59
16000635
J Neuropathol Exp Neurol. 1997 Sep;56(9):965-73
9291938
Free Radic Biol Med. 2001 May 15;30(10):1163-70
11369507
Brain Res. 1992 May 22;581(1):168-70
1379868
Ann Neurol. 1995 Mar;37(3):287-8
7695227
J Biol Chem. 1993 Nov 5;268(31):23289-96
8226852
Nature. 2006 Jun 15;441(7095):880-4
16625205
J Neurosci. 1998 Dec 1;18(23):9790-9
9822738
J Neurosci Res. 2009 Apr;87(5):1250-9
18951528
J Neurobiol. 1992 Nov;23(9):1261-76
1361523
Science. 2000 Nov 3;290(5493):985-9
11062131
Trends Neurosci. 2000 Sep;23(9):410-1
10941188
Neurobiol Dis. 2002 Aug;10(3):258-67
12270688
J Neurochem. 2009 Mar;108(6):1561-74
19166511
Neurosci Lett. 2001 Nov 27;315(3):125-8
11716979
Mol Cell. 2001 Sep;8(3):613-21
11583623
J Neurosci. 2000 Sep 1;20(17):6365-73
10964942
Neuron. 2004 Nov 18;44(4):601-7
15541309
Int Rev Neurobiol. 1971;14:49-124
4948651
J Biol Chem. 2005 Jun 3;280(22):21418-26
15799973
Nature. 2006 Jun 15;441(7095):885-9
16625204
Hum Mol Genet. 2006 May 1;15(9):1437-49
16551656
Cell. 1995 Jan 27;80(2):285-91
7834748
Free Radic Biol Med. 2003 Jun 1;34(11):1383-9
12757848
Nat Genet. 1992 Dec;2(4):318-23
1303287
Annu Rev Genet. 1999;33:29-55
10690403
Cell. 1996 Nov 15;87(4):629-38
8929532
Neurodegener Dis. 2004;1(1):9-19
16908969
J Biol Chem. 1999 Feb 26;274(9):5823-9
10026204
Nat Cell Biol. 2001 Feb;3(2):E43-6
11175758
Exp Neurol. 1995 Jun;133(2):225-30
7544290
J Mol Cell Cardiol. 2009 Jun;46(6):821-31
19265700
J Cell Biol. 2002 Feb 4;156(3):519-29
11815632
Cell Cycle. 2008 Oct;7(20):3225-34
18927501
Ann Neurol. 1999 Nov;46(5):787-90
10553999
Cell. 2008 Dec 26;135(7):1311-23
19109899
Neuron. 2002 May 16;34(4):521-33
12062037
J Cell Biol. 1999 Mar 8;144(5):891-901
10085289
J Biol Chem. 2000 Apr 21;275(16):11553-60
10766769
Neuropathology. 2005 Dec;25(4):381-7
16382789
Acta Physiol Scand. 2003 Oct;179(2):123-35
14510775
Ann Neurol. 1998 May;43(5):673-6
9585365
Biochem Soc Symp. 1999;66:17-25
10989653
Biochem Biophys Res Commun. 1991 Aug 30;179(1):39-45
1679329
Acta Neuropathol. 1999 Apr;97(4):413-5
10208282
JAMA. 1989 Nov 10;262(18):2551-6
2810583
Free Radic Biol Med. 2002 May 1;32(9):797-803
11978481
J Cell Biol. 2008 Dec 1;183(5):795-803
19029340
Neurobiol Dis. 2002 Nov;11(2):341-54
12505426
Genes Dev. 1998 Oct 1;12(19):2973-83
9765199
Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9256-61
12855764
Nature. 2003 Aug 21;424(6951):952-6
12931191
Teratology. 1973 Jun;7(3):253-66
4807128
Brain Res. 2001 Mar 16;894(2):327-31
11251210
Am J Pathol. 1995 Jan;146(1):3-15
7856735
J Neurol Neurosurg Psychiatry. 2008 Apr;79(4):368-76
18344392
Ann Neurol. 1997 Oct;42(4):644-54
9382477
Cancer Res. 1996 Jun 1;56(11):2649-54
8653711
Nat Rev Mol Cell Biol. 2008 Jan;9(1):47-59
18097445
Lancet. 1991 Apr 20;337(8747):978-9
1678058
Hum Mol Genet. 2000 Nov 1;9(18):2683-9
11063727
FASEB J. 2005 Dec;19(14):2040-1
16210396
J Biol Chem. 2006 Apr 28;281(17):11658-68
16517608
J Alzheimers Dis. 2009;16(3):565-75
19276551
Neurobiol Dis. 2005 Apr;18(3):492-8
15755676
Neuroreport. 2002 Oct 7;13(14):1753-7
12395117
Aging Cell. 2004 Feb;3(1):3-6
14965348
J Neurol Sci. 2001 Oct 15;191(1-2):25-33
11676989
Science. 1999 Dec 24;286(5449):2498-500
10617463
Proc Natl Acad Sci U S A. 2004 Oct 12;101(41):14966-71
15465911
Neuron. 2004 Jul 8;43(1):5-17
15233913
J Neurochem. 1993 May;60(5):1953-5
8097239
Neurobiol Dis. 2000 Aug;7(4):225-39
10964595
Neuropsychiatr Dis Treat. 2009;5:577-95
19966906
J Neurol Sci. 2001 Jan 1;182(2):151-9
11137521
Proc Natl Acad Sci U S A. 2008 Mar 11;105(10):4022-7
18296640
Neuroscience. 1998 Sep;86(1):191-209
9692754
J Comp Neurol. 1997 Feb 3;378(1):70-87
9120055
Neuropathol Appl Neurobiol. 2001 Aug;27(4):257-74
11532157
Cell Death Differ. 2006 Oct;13(10):1675-85
16410794
Curr Med Chem. 2003 Aug;10(16):1507-25
12871123
Science. 2000 Jul 14;289(5477):304-6
10894779
Trends Genet. 1998 Oct;14(10):410-6
9820030
Nature. 1999 Feb 4;397(6718):441-6
9989411
Hum Mol Genet. 2007 Jun 1;16(11):1319-26
17409193
J Neuropathol Exp Neurol. 1998 Jun;57(6):571-87
9630237
Biochim Biophys Acta. 1995 Jul 17;1241(2):139-76
7640294
Proc Natl Acad Sci U S A. 2006 Sep 12;103(37):13860-5
16945901
J Biol Chem. 2003 Sep 19;278(38):36588-95
12851414
J Neurosci. 2005 Nov 23;25(47):10913-21
16306404
Prog Neurobiol. 2008 May;85(1):94-134
18282652
J Neurochem. 2004 Feb;88(4):821-6
14756802
Arch Neurol. 2003 Mar;60(3):369-76
12633148
Am J Pathol. 2008 Sep;173(3):665-81
18688038
Nat Genet. 1997 Jul;16(3):226-34
9207786
J Neurosci. 2000 May 1;20(9):3214-20
10777786
Science. 2003 Jul 25;301(5632):513-7
12881569
J Mol Med (Berl). 2005 Feb;83(2):110-20
15624111
Hum Mol Genet. 1995 Dec;4(12):2373-7
8634712
Science. 1997 Feb 21;275(5303):1129-32
9027314
Am J Pathol. 2004 Aug;165(2):523-31
15277226
Neurobiol Dis. 2000 Dec;7(6 Pt B):613-22
11114260
Ann Neurol. 2004 Sep;56(3):424-7
15349870
Carcinogenesis. 1990 May;11(5):847-53
2139818
Curr Med Chem. 2003 Aug;10(16):1485-506
12871122
Eur J Neurosci. 2008 Feb;27(4):937-46
18333964
Ann Neurol. 2003 Sep;54(3):393-8
12953274
Ann Neurol. 1990 May;27(5):457-64
2360787
Anat Embryol (Berl). 1990;181(3):195-213
2186664
Proc Natl Acad Sci U S A. 2005 Feb 8;102(6):2174-9
15684050
Biochem J. 2002 Oct 15;367(Pt 2):541-8
12149099
Nature. 2009 Feb 19;457(7232):981-9
19225519
Nat Genet. 1992 Dec;2(4):324-9
1303288
Proc Natl Acad Sci U S A. 1986 Jun;83(11):4044-8
2424016
Biochem Biophys Res Commun. 2005 Dec 2;337(4):1133-8
16226715
Science. 1989 Jul 28;245(4916):417-20
2474201
Proc Natl Acad Sci U S A. 2002 Apr 30;99(9):6364-9
11959919
Nature. 1980 Apr 10;284(5756):555-6
6245367
Neurochem Res. 2003 Jan;28(1):15-27
12587660
Ann Neurol. 1998 Jan;43(1):110-6
9450776
Nature. 1998 Apr 9;392(6676):605-8
9560156
Biochem J. 1994 Jun 15;300 ( Pt 3):865-70
8010971
Neurobiol Dis. 2001 Apr;8(2):207-19
11300718
Ann Neurol. 1996 Feb;39(2):203-16
8967752
Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):7951-5
8367446
Brain Res. 1998 Jan 12;780(2):260-9
9507158
Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):571-6
10639120
Cell Death Differ. 2002 Apr;9(4):367-93
11965491
Cell. 1997 Oct 31;91(3):325-34
9363941
Oncogene. 1998 Dec 24;17(25):3247-59
9916987
Neurosci Lett. 2002 Mar 8;320(3):146-50
11852183
Neurology. 1984 Jul;34(7):939-44
6610841
Neurosci Lett. 2001 May 25;304(3):165-8
11343828
Am J Pathol. 2000 Jul;157(1):331-9
10880403
Exp Neurol. 2003 Jun;181(2):149-58
12781988
J Cell Sci. 2000 May;113 ( Pt 10):1661-70
10769197
J Neurochem. 2002 Apr;81(2):301-6
12064477
J Neurosci. 2002 Nov 15;22(22):9733-41
12427828
Neurobiol Aging. 2008 Apr;29(4):574-85
17174013
Brain. 2000 Jul;123 ( Pt 7):1339-48
10869047
Brain Struct Funct. 2010 Mar;214(2-3):219-34
19888600
J Neurosci. 2002 Mar 15;22(6):RC215
11886899
J Neurosci. 2008 Nov 19;28(47):12305-17
19020024
J Cell Biol. 2001 Jun 11;153(6):1265-76
11402069
Nat Rev Mol Cell Biol. 2003 Jul;4(7):552-65
12838338
Neuron. 1995 Oct;15(4):961-73
7576644
Histol Histopathol. 1997 Jan;12(1):25-31
9046040
Science. 2004 May 21;304(5674):1158-60
15087508
J Neurochem. 2006 Aug;98(3):951-61
16771836
Neurology. 2006 May 23;66(10 Suppl 4):S10-23
16717248
J Neurobiol. 2002 Apr;51(1):9-23
11920724
J Neurosci. 1996 Jul 15;16(14):4491-500
8699259
J Neuropathol Exp Neurol. 1999 Sep;58(9):1020-6
10499444
Nature. 2000 Jan 6;403(6765):98-103
10638761
Acta Neuropathol. 2008 Jan;115(1):5-38
18038275
Science. 2004 Apr 16;304(5669):448-52
15087549
Mol Cell Neurosci. 1999 Sep;14(3):180-98
10576889
Science. 1966 Nov 4;154(3749):604-12
5332319
J Neurosci. 2009 Feb 18;29(7):1962-76
19228951
EMBO J. 1999 Jan 4;18(1):167-78
9878060
Proc Natl Acad Sci U S A. 2007 May 1;104(18):7558-63
17463082
Neuroscience. 2003;117(1):19-28
12605888
Autophagy. 2008 May;4(4):527-30
18367867
Br J Cancer. 1972 Aug;26(4):239-57
4561027
Nat Cell Biol. 2007 May;9(5):550-5
17417626
Biochem Biophys Res Commun. 2005 Jun 10;331(3):843-50
15865940
Science. 2003 Nov 7;302(5647):1036-8
14500851
Neuroreport. 2004 Apr 29;15(6):939-43
15076711
FEBS J. 2006 May;273(10):2077-99
16649987
Free Radic Biol Med. 2005 Aug 15;39(4):453-62
16043017
Int J Biochem Cell Biol. 2002 Nov;34(11):1372-81
12200032
Biochemistry (Mosc). 2007 Oct;72(10):1115-26
18021069
Nature. 1998 Oct 22;395(6704):755-6
9796810
Mol Pharmacol. 2009 Mar;75(3):478-89
19060114
Hum Mol Genet. 2008 Jul 1;17(13):1988-93
18364387
EMBO J. 1998 Apr 15;17(8):2215-23
9545235
Proc Natl Acad Sci U S A. 2005 Apr 19;102(16):5703-8
15824318
Science. 2003 Apr 4;300(5616):135-9
12624178
J Neurosci Res. 2005 Dec 1;82(5):592-608
16247803
Nature. 2004 Jan 29;427(6973):461-5
14749836
Cell. 1997 Apr 18;89(2):175-84
9108473
Nature. 1996 May 23;381(6580):335-41
8692274
J Neurosci. 1998 Feb 15;18(4):1363-73
9454845
J Cell Biol. 1997 Dec 1;139(5):1281-92
9382873
J Neurosci. 1988 Aug;8(8):2804-15
3411354
J Comp Neurol. 1999 Jun 14;408(4):461-76
10340498
J Neurosci. 1998 May 1;18(9):3241-50
9547233
J Biol Chem. 2004 Apr 9;279(15):15499-504
14734542
Nat Rev Cancer. 2002 Sep;2(9):647-56
12209154
Biochim Biophys Acta. 2008 Jul-Aug;1777(7-8):946-52
18407825
Hum Mol Genet. 2007 Oct 15;16 Spec No. 2:R233-42
17911166
Neurobiol Dis. 2007 Oct;28(1):83-9
17689254
Neurology. 1993 Jan;43(1):13-20
8423876
Eur J Neurosci. 2007 Jun;25(12):3583-96
17610578
J Mol Neurosci. 1993 Fall;4(3):149-59
8292488
J Clin Immunol. 2003 Sep;23(5):355-61
14601643
J Neurochem. 1999 Jan;72(1):292-301
9886081
Cell Death Differ. 2001 Jun;8(6):569-81
11536007
Neurobiol Dis. 2002 Oct;11(1):2-19
12460542
Annu Rev Med. 1996;47:387-400
8712790
Cereb Cortex. 2009 Jun;19(6):1273-93
18820287
J Neuropathol Exp Neurol. 2001 Sep;60(9):839-46
11556540
Am J Pathol. 1997 Jan;150(1):119-31
9006329
Physiol Rev. 2007 Jan;87(1):315-424
17237348
Science. 2004 Feb 13;303(5660):1010-4
14963330
Curr Pharm Des. 2006;12(18):2249-70
16787253
J Biol Chem. 2002 Mar 8;277(10):7720-5
11756426
J Biol Chem. 2002 Aug 23;277(34):31243-8
12063261
Brain. 2004 Jun;127(Pt 6):1237-51
15130949
Biochim Biophys Acta. 1999 Oct 13;1452(1):68-78
10525161
Trends Genet. 2002 Oct;18(10):537
12350344
J Neurosci. 1996 Mar 1;16(5):1710-9
8774439
Annu Rev Biochem. 1995;64:97-112
7574505
Eur J Biochem. 1999 Jul;263(2):353-9
10406942
Annu Rev Neurosci. 1997;20:245-67
9056714
J Neurochem. 2001 Apr;77(1):220-8
11279278
J Neurosci. 2005 Jul 27;25(30):6962-70
16049172
J Comp Neurol. 1997 Feb 3;378(1):88-104
9120056
Neurochem Res. 2002 Oct;27(10):1093-104
12462407
Biochim Biophys Acta. 2003 Mar 17;1603(2):113-28
12618311
Biochim Biophys Acta. 2010 Jan;1802(1):186-97
19651206
Neuron. 1995 Jun;14(6):1105-16
7605627
AMA Arch Ophthalmol. 1957 Aug;58(2):193-201
13443577
Am J Pathol. 1994 Dec;145(6):1271-9
7992831
J Biol Chem. 2003 Oct 31;278(44):43628-35
12930822
Am J Hum Genet. 2009 Jan;84(1):85-8
19118816
Nature. 1995 Jun 29;375(6534):754-60
7596406
Neurobiol Aging. 1998 Sep-Oct;19(5):371-7
9880038
Exp Neurol. 2006 Mar;198(1):25-30
16126198
J Biol Chem. 2000 Apr 21;275(16):12321-5
10766872
Biochim Biophys Acta. 1996 Oct 11;1313(3):173-8
8898851
Biol Rev Camb Philos Soc. 1951 Feb;26(1):59-86
24540363
Brain Res Brain Res Rev. 2005 Dec 15;50(2):244-57
16216332
Proc Natl Acad Sci U S A. 1993 Feb 1;90(3):980-4
8430112
Neuron. 2003 Jul 31;39(3):409-21
12895417
J Cell Biol. 1998 Mar 23;140(6):1485-95
9508780
Biochem Biophys Res Commun. 2004 Jul 23;320(2):389-97
15219840
Cell. 1998 Aug 21;94(4):491-501
9727492
J Cell Biol. 1976 Feb;68(2):339-56
942724
J Biol Chem. 2001 Oct 19;276(42):38388-93
11507097
Science. 1997 Jul 18;277(5324):373-6
9219695
Annu Rev Biochem. 1998;67:425-79
9759494
Exp Physiol. 2003 Jan;88(1):149-54
12525863
Neurochem Int. 2002 May;40(6):543-51
11850111
Neuroscience. 2006;139(3):791-4
16504409
Exp Neurol. 2009 Aug;218(2):333-46
19272377
J Cereb Blood Flow Metab. 2000 Jan;20(1):153-67
10616804
Ann N Y Acad Sci. 2000 Jun;908:255-9
10911964
Hum Mol Genet. 2007 Nov 15;16(22):2720-2728
17725983
Curr Opin Neurobiol. 2004 Jun;14(3):384-9
15194120
Mol Cell. 2007 Jun 8;26(5):675-87
17560373
J Neurosci. 2009 Jan 28;29(4):1011-6
19176810
Oncogene. 2000 Jan 13;19(2):307-14
10645010
J Neurosci. 2001 Oct 15;21(20):8053-61
11588178
J Neurochem. 2007 Jul;102(1):170-8
17394546
Nat Cell Biol. 2004 May;6(5):443-50
15077116
Nature. 1993 Aug 12;364(6438):584
8350919
Brain Res Mol Brain Res. 2001 Mar 31;88(1-2):94-102
11295235
Proc Natl Acad Sci U S A. 1995 May 9;92(10):4507-11
7753834
Brain Res. 2001 Apr 20;898(2):350-7
11306022
Proc Natl Acad Sci U S A. 2000 Apr 25;97(9):4897-902
10781096
J Biol Chem. 2001 Oct 19;276(42):39206-12
11507092
Neurosci Lett. 1995 Oct 20;199(2):152-4
8584246
J Neurol Sci. 2006 May 15;244(1-2):41-58
16487542
Curr Biol. 2002 Sep 17;12(18):1595-600
12372252
Proc Natl Acad Sci U S A. 1999 May 11;96(10):5752-7
10318956