title: Neuroprotective therapy in Parkinson's disease: current status and new directions from experimental and genetic clues.
abstract: Despite successful treatment of Parkinson's disease (PD) with a wide variety of symptomatic therapy, the disease continues to progress and drug-resistance symptoms become the predominant factors producing the disability of PD patients. Neuroprotective therapies have been tested, but clinically effective drugs have not been found yet. New insights gained from studies of genetic forms of PD point to the common pathogenic mechanisms that have been suspected in sporadic forms of the disease and may provide new approaches for the future neuroprotective therapies.
authors.affiliation: Committees on Neurobiology and Molecular Medicine, Departments of Neurology and Neurobiology, Pharmacology, & Physiology, The University of Chicago, USA.
authors.forename: William
authors.initials: W
authors.lastname: Lin
authors.forename: Un Jung
authors.initials: UJ
authors.lastname: Kang
references.citation: Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):8968-73
references.pmid: 12084935
references.citation: Curr Opin Neurol. 2000 Aug;13(4):427-30
references.pmid: 10970060
references.citation: Science. 1997 Jun 27;276(5321):2045-7
references.pmid: 9197268
references.citation: Free Radic Biol Med. 1993 Aug;15(2):169-79
references.pmid: 8397142
references.citation: Nature. 1998 Oct 1;395(6701):451-2
references.pmid: 9774100
references.citation: Ann Neurol. 2004 Apr;55(4):512-21
references.pmid: 15048890
references.citation: Mol Ther. 2005 Jan;11(1):80-8
references.pmid: 15585408
references.citation: Science. 2003 Jan 10;299(5604):256-9
references.pmid: 12446870
references.citation: Ann N Y Acad Sci. 2003 Jun;991:189-98
references.pmid: 12846987
references.citation: Life Sci. 1987 Feb 23;40(8):721-9
references.pmid: 3100899
references.citation: Am J Hum Genet. 2005 Aug;77(2):252-64
references.pmid: 15986317
references.citation: J Biol Chem. 1986 Jun 15;261(17):7585-7
references.pmid: 3486869
references.citation: Neurology. 2005 May 10;64(9):1655-6
references.pmid: 15883340
references.citation: Nat Genet. 1999 Sep;23(1):47-51
references.pmid: 10471497
references.citation: JAMA. 2000 May 24-31;283(20):2674-9
references.pmid: 10819950
references.citation: Proc Natl Acad Sci U S A. 2004 Sep 21;101(38):13891-6
references.pmid: 15353588
references.citation: Science. 2003 Oct 31;302(5646):841
references.pmid: 14593171
references.citation: Neurology. 1992 Apr;42(4 Suppl 4):13-26; discussion 41-8
references.pmid: 1584429
references.citation: Mol Cell. 2004 Apr 9;14(1):81-93
references.pmid: 15068805
references.citation: Proc Natl Acad Sci U S A. 2000 Nov 21;97(24):13354-9
references.pmid: 11078524
references.citation: N Engl J Med. 2004 Dec 9;351(24):2498-508
references.pmid: 15590952
references.citation: N Engl J Med. 1993 Jan 21;328(3):176-83
references.pmid: 8417384
references.citation: Arch Neurol. 2004 Apr;61(4):561-6
references.pmid: 15096406
references.citation: Adv Neurol. 1993;60:600-8
references.pmid: 8380528
references.citation: Biochemistry. 1998 Mar 10;37(10):3358-68
references.pmid: 9521656
references.citation: J Biol Chem. 2002 Jan 18;277(3):1641-4
references.pmid: 11707429
references.citation: Arch Neurol. 2003 Aug;60(8):1059-64
references.pmid: 12925360
references.citation: J Neurol Neurosurg Psychiatry. 2005 Sep;76(9):1217-21
references.pmid: 16107354
references.citation: Ann Neurol. 2003 Jul;54(1):93-101
references.pmid: 12838524
references.citation: Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9074-8
references.pmid: 1409604
references.citation: J Biol Chem. 2001 Sep 14;276(37):34402-7
references.pmid: 11447224
references.citation: Nat Med. 2002 Jun;8(6):600-6
references.pmid: 12042811
references.citation: Neurol Clin. 1996 May;14(2):317-35
references.pmid: 8827174
references.citation: Hum Mol Genet. 2001 Apr 15;10(9):919-26
references.pmid: 11309365
references.citation: Nat Genet. 1998 Feb;18(2):106-8
references.pmid: 9462735
references.citation: Neurology. 2002 Feb 26;58(4):581-8
references.pmid: 11865136
references.citation: Neurology. 2005 Feb 22;64(4):664-9
references.pmid: 15728289
references.citation: Exp Neurol. 1999 May;157(1):142-9
references.pmid: 10222117
references.citation: Neurology. 2001 Jun 12;56(11):1559-64
references.pmid: 11402115
references.citation: Arch Neurol. 1989 Oct;46(10):1052-60
references.pmid: 2508608
references.citation: Ann Neurol. 1996 Jan;39(1):29-36
references.pmid: 8572663
references.citation: Ann Neurol. 2003;53 Suppl 3:S149-57; discussion S157-9
references.pmid: 12666106
references.citation: Neuron. 2005 Feb 17;45(4):489-96
references.pmid: 15721235
references.citation: J Biol Chem. 2004 May 14;279(20):20699-707
references.pmid: 14742431
references.citation: Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5473-8
references.pmid: 12702778
references.citation: Proc Natl Acad Sci U S A. 1985 Apr;82(7):2173-7
references.pmid: 3872460
references.citation: J Neural Transm Suppl. 1999;56:1-29
references.pmid: 10370901
references.citation: Ann Neurol. 1997 Aug;42(2):261-4
references.pmid: 9266740
references.citation: PLoS Biol. 2004 Nov;2(11):e362
references.pmid: 15502874
references.citation: Science. 2000 Feb 18;287(5456):1265-9
references.pmid: 10678833
references.citation: Brain. 1992 Apr;115 ( Pt 2):333-42
references.pmid: 1606472
references.citation: JAMA. 2002 Apr 3;287(13):1653-61
references.pmid: 11926889
references.citation: J Biol Chem. 2004 Apr 30;279(18):18614-22
references.pmid: 14985362
references.citation: Neuroreport. 1999 Feb 5;10(2):427-9
references.pmid: 10203348
references.citation: Curr Opin Neurol. 2005 Aug;18(4):363-9
references.pmid: 16003110
references.citation: Neuron. 2004 Nov 18;44(4):601-7
references.pmid: 15541309
references.citation: Lancet. 1989 Jun 3;1(8649):1269
references.pmid: 2566813
references.citation: J Biol Chem. 2005 Jun 3;280(22):21418-26
references.pmid: 15799973
references.citation: Brain Res. 1998 Feb 2;783(1):109-14
references.pmid: 9479058
references.citation: Ann Neurol. 2004 Feb;55(2):164-73
references.pmid: 14755719
references.citation: Neurology. 2001 Feb 27;56(4):455-62
references.pmid: 11222787
references.citation: J Neurosci Res. 2005 Jan 1-15;79(1-2):172-9
references.pmid: 15573406
references.citation: Brain. 1991 Oct;114 ( Pt 5):2283-301
references.pmid: 1933245
references.citation: Prog Neuropsychopharmacol Biol Psychiatry. 1996 Oct;20(7):1159-70
references.pmid: 8938817
references.citation: Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9256-61
references.pmid: 12855764
references.citation: N Engl J Med. 1989 Nov 16;321(20):1364-71
references.pmid: 2509910
references.citation: J Neurosci. 2001 Dec 15;21(24):9549-60
references.pmid: 11739566
references.citation: Neurobiol Dis. 2005 Feb;18(1):19-31
references.pmid: 15649693
references.citation: Neurobiol Dis. 2002 Jul;10(2):119-27
references.pmid: 12127150
references.citation: Brain Res. 1997 Apr 4;753(1):157-62
references.pmid: 9125443
references.citation: J Neurochem. 2003 Feb;84(3):491-502
references.pmid: 12558969
references.citation: Am J Hum Genet. 1997 Mar;60(3):588-96
references.pmid: 9042918
references.citation: Science. 2001 Nov 9;294(5545):1346-9
references.pmid: 11701929
references.citation: Neurol Clin. 2004 Oct;22(3 Suppl):S1-S17
references.pmid: 15501359
references.citation: Nature. 1998 Apr 9;392(6676):605-8
references.pmid: 9560156
references.citation: Biochemistry. 1996 May 28;35(21):6735-44
references.pmid: 8639624
references.citation: Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):571-6
references.pmid: 10639120
references.citation: Lancet Neurol. 2005 Jun;4(6):362-5
references.pmid: 15907740
references.citation: J Neurochem. 2001 Jul;78(2):374-83
references.pmid: 11461973
references.citation: Ann Neurol. 2005 Feb;57(2):197-203
references.pmid: 15668964
references.citation: Neurology. 2003 Dec 9;61(11):1557-61
references.pmid: 14663042
references.citation: Neuron. 2002 Dec 19;36(6):1007-19
references.pmid: 12495618
references.citation: Brain Res. 2001 Jul 6;906(1-2):135-42
references.pmid: 11430870
references.citation: Mov Disord. 2005 Jun;20(6):653-64
references.pmid: 15719422
references.citation: Mol Pharmacol. 2000 Aug;58(2):271-8
references.pmid: 10908294
references.citation: Science. 2004 May 21;304(5674):1158-60
references.pmid: 15087508
references.citation: J Neurochem. 1999 Dec;73(6):2546-54
references.pmid: 10582617
references.citation: Trends Pharmacol Sci. 1999 Oct;20(10):424-9
references.pmid: 10498956
references.citation: J Biol Chem. 2004 Dec 10;279(50):51783-92
references.pmid: 15469939
references.citation: J Biol Chem. 1998 Feb 6;273(6):3756-64
references.pmid: 9452508
references.citation: Proc Natl Acad Sci U S A. 2005 Apr 19;102(16):5703-8
references.pmid: 15824318
references.citation: Science. 2002 Feb 1;295(5556):865-8
references.pmid: 11823645
references.citation: J Biol Chem. 2005 Jan 28;280(4):2873-8
references.pmid: 15556931
references.citation: Arch Neurol. 2002 Oct;59(10):1541-50
references.pmid: 12374491
references.citation: Trends Neurosci. 2001 Nov;24(11 Suppl):S49-55
references.pmid: 11881746
references.citation: Free Radic Res. 2001 Sep;35(3):301-10
references.pmid: 11697128
references.citation: Eur Neurol. 2005;53(1):15-21
references.pmid: 15627775
references.citation: J Neural Transm (Vienna). 2004 Dec;111(12):1543-73
references.pmid: 15455214
references.citation: J Biol Chem. 2003 Oct 31;278(44):43628-35
references.pmid: 12930822
references.citation: Neurology. 2003 Apr 22;60(8):1234-40
references.pmid: 12707423
references.citation: J Pharmacol Exp Ther. 1999 Feb;288(2):421-7
references.pmid: 9918541
references.citation: Exp Neurol. 1999 Feb;155(2):268-73
references.pmid: 10072302
references.citation: J Neurochem. 2000 Jun;74(6):2305-14
references.pmid: 10820190
references.citation: J Biol Chem. 1999 Jun 4;274(23):16188-97
references.pmid: 10347173
references.citation: Nat Genet. 2000 Jul;25(3):302-5
references.pmid: 10888878
references.citation: Nat Neurosci. 2000 Dec;3(12):1301-6
references.pmid: 11100151
references.citation: Nat Rev Mol Cell Biol. 2003 Mar;4(3):181-91
references.pmid: 12612637