title: Oxidative stress and the pathogenesis of Alzheimer's disease.
abstract: Alzheimer's disease (AD) is the most common neurodegenerative disease that causes dementia in the elderly. Patients with AD suffer a gradual deterioration of memory and other cognitive functions, which eventually leads to a complete incapacity and death. A complicated array of molecular events has been implicated in the pathogenesis of AD. The major pathological characteristics of AD brains are the presence of senile plaques, neurofibrillary tangles, and neuronal loss. Growing evidence has demonstrated that oxidative stress is an important factor contributing to the initiation and progression of AD. However, the mechanisms that lead to the disruption of redox balance and the sources of free radicals remain elusive. The excessive reactive oxygen species may be generated from mechanisms such as mitochondria dysfunction and/or aberrant accumulation of transition metals, while the abnormal accumulation of Abeta and tau proteins appears to promote the redox imbalance. The resulted oxidative stress has been implicated in Abeta- or tau-induced neurotoxicity. In addition, evidence has suggested that oxidative stress may augment the production and aggregation of Abeta and facilitate the phosphorylation and polymerization of tau, thus forming a vicious cycle that promotes the initiation and progression of AD.
authors: Department of Bioengineering, Harbin Institute of Technology at Weihai, Weihai, Shandong 264209, China. ywz12@yahoo.com
authors: Yan
authors: Y
authors: Zhao
authors: Baolu
authors: B
authors: Zhao
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D006801:Humans; D018384:Oxidative Stress / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species
references: Exp Gerontol. 2000 Jul;35(4):445-51
references: 10959032
references: Ann Neurol. 1994 Nov;36(5):747-51
references: 7979220
references: J Neurochem. 1998 Nov;71(5):2034-40
references: 9798928
references: J Neurochem. 2001 Jan;76(2):435-41
references: 11208906
references: Mol Neurobiol. 2010 Jun;41(2-3):107-14
references: 20217279
references: Neurobiol Dis. 2004 Oct;17(1):108-13
references: 15350971
references: J Biol Chem. 2002 Nov 22;277(47):45518-28
references: 12198135
references: Neurobiol Dis. 2010 Mar;37(3):731-7
references: 20034567
references: J Neuropathol Exp Neurol. 2000 Oct;59(10):880-8
references: 11079778
references: FASEB J. 2009 Dec;23(12):4207-17
references: 19679638
references: Biochemistry. 2000 Nov 21;39(46):14203-10
references: 11087369
references: Lancet Neurol. 2008 Sep;7(9):812-26
references: 18667359
references: Free Radic Biol Med. 2001 Jan 1;30(1):119-28
references: 11134902
references: Adv Exp Med Biol. 2007;595:197-212
references: 17569212
references: J Neurochem. 1994 Dec;63(6):2179-84
references: 7964738
references: Neuromolecular Med. 2009;11(4):223-38
references: 19946766
references: Brain Res Bull. 2008 Sep 5;77(1):55-60
references: 18639746
references: Neurobiol Dis. 2002 Aug;10(3):279-88
references: 12270690
references: Biochim Biophys Acta. 2006 May-Jun;1757(5-6):553-61
references: 16678117
references: J Alzheimers Dis. 2012;28(1):173-82
references: 21971408
references: Science. 2006 Nov 3;314(5800):781-4
references: 17082448
references: FEBS Lett. 1997 Jun 2;409(1):57-62
references: 9199504
references: Proc Natl Acad Sci U S A. 2009 Nov 24;106(47):20057-62
references: 19897719
references: Age Ageing. 2007 Nov;36(6):619-24
references: 17965036
references: Am J Pathol. 1995 Feb;146(2):357-67
references: 7856748
references: J Biol Chem. 2005 Jun 24;280(25):23802-14
references: 15831501
references: Brain Res Bull. 2001 May 15;55(2):175-85
references: 11470313
references: J Neuropathol Exp Neurol. 2010 Feb;69(2):155-67
references: 20084018
references: Neurosci Lett. 1996 Oct 18;217(2-3):125-8
references: 8916088
references: J Biol Chem. 1999 Dec 24;274(52):37111-6
references: 10601271
references: FASEB J. 2004 Jun;18(9):1034-6
references: 15059975
references: J Biol Chem. 2011 Mar 11;286(10):8252-8262
references: 21177866
references: Am J Pathol. 2006 May;168(5):1608-18
references: 16651627
references: J Neurosci. 2001 May 1;21(9):3017-23
references: 11312286
references: Br J Pharmacol. 2011 May;163(2):211-9
references: 21232050
references: J Neurosci. 1999 Jun 1;19(11):RC10
references: 10341271
references: J Biol Chem. 2002 Nov 22;277(47):44670-6
references: 12215434
references: Mech Ageing Dev. 2001 Jul 15;122(9):945-62
references: 11348660
references: J Biol Chem. 1998 May 22;273(21):12817-26
references: 9582309
references: J Neurochem. 2007 Jun;101(5):1172-84
references: 17286590
references: FASEB J. 2009 Aug;23(8):2459-66
references: 19346295
references: J Biol Chem. 2008 Jun 20;283(25):17721-30
references: 18436531
references: Neurobiol Aging. 2010 Jan;31(1):74-87
references: 18378045
references: N Engl J Med. 2010 Jan 28;362(4):329-44
references: 20107219
references: Arch Med Res. 2001 Sep-Oct;32(5):367-81
references: 11578751
references: Neurobiol Aging. 2002 Nov-Dec;23(6):1031-8
references: 12470799
references: Science. 2001 Aug 24;293(5534):1449-54
references: 11520976
references: Neuron. 2001 Jun;30(3):665-76
references: 11430801
references: Free Radic Biol Med. 2001 Feb 15;30(4):447-50
references: 11182300
references: Arch Neurol. 2003 Dec;60(12):1685-91
references: 14676042
references: J Neurol Sci. 1998 Jun 11;158(1):47-52
references: 9667777
references: Free Radic Biol Med. 2007 Nov 15;43(10):1351-71
references: 17936181
references: Neurology. 1995 Aug;45(8):1594-601
references: 7644059
references: Science. 2001 Aug 24;293(5534):1487-91
references: 11520987
references: Science. 2001 Aug 24;293(5534):1491-5
references: 11520988
references: Antioxid Redox Signal. 2010 Apr 1;12(7):819-27
references: 19769463
references: Acta Neuropathol. 2009 Jul;118(1):53-69
references: 19184068
references: Nat Med. 2003 Jan;9(1):3-4
references: 12514700
references: Hum Mol Genet. 2006 May 1;15(9):1437-49
references: 16551656
references: J Biol Chem. 2009 Feb 20;284(8):4755-9
references: 18957434
references: Biometals. 2012 Aug;25(4):825-35
references: 22639188
references: Neuroscientist. 2004 Oct;10(5):432-42
references: 15359010
references: Science. 1994 Sep 2;265(5177):1464-7
references: 8073293
references: Biochem Biophys Res Commun. 2001 Feb 23;281(2):468-74
references: 11181071
references: Biochem Biophys Res Commun. 2006 Nov 24;350(3):530-6
references: 17026966
references: Free Radic Biol Med. 2002 May 1;32(9):797-803
references: 11978481
references: Int J Dev Neurosci. 2004 Nov;22(7):475-84
references: 15465277
references: FASEB J. 2005 Dec;19(14):2040-1
references: 16210396
references: J Neurosci. 2003 Jul 2;23(13):5531-5
references: 12843253
references: J Neuropathol Exp Neurol. 2006 Jul;65(7):631-41
references: 16825950
references: FASEB J. 2011 Nov;25(11):4063-72
references: 21825035
references: J Neurosci. 2002 Jun 15;22(12):4833-41
references: 12077180
references: J Biol Chem. 2002 Oct 25;277(43):40302-8
references: 12192006
references: Brain Res. 1999 Sep 25;842(2):439-44
references: 10526140
references: J Neurochem. 2003 Apr;85(1):87-93
references: 12641730
references: J Neurosci Res. 2010 Apr;88(5):1137-45
references: 19885829
references: J Neuropathol Exp Neurol. 2006 May;65(5):455-64
references: 16772869
references: FASEB J. 2006 Jun;20(8):1212-4
references: 16627626
references: J Biol Chem. 2003 May 9;278(19):17401-7
references: 12611883
references: Eur J Neurosci. 2006 Aug;24(4):1085-90
references: 16930434
references: J Neurosci. 2005 Feb 2;25(5):1149-58
references: 15689551
references: J Cell Biol. 2002 Mar 18;156(6):1051-63
references: 11901170
references: Biochem J. 1997 May 1;323 ( Pt 3):577-91
references: 9169588
references: Biochemistry. 1999 Jun 15;38(24):7609-16
references: 10386999
references: Cell. 1994 Jun 17;77(6):817-27
references: 8004671
references: Alzheimers Dement. 2010 Mar;6(2):158-94
references: 20298981
references: J Nutr. 2008 Aug;138(8):1578S-1583S
references: 18641210
references: Trends Pharmacol Sci. 2008 Dec;29(12):609-15
references: 18838179
references: Exp Neurol. 1998 Mar;150(1):40-4
references: 9514828
references: J Neurosci. 1999 Mar 15;19(6):1959-64
references: 10066249
references: J Neurochem. 2008 Feb;104(3):683-95
references: 18005001
references: J Neurochem. 2004 Jun;89(5):1308-12
references: 15147524
references: J Biol Chem. 2001 Jun 8;276(23):20466-73
references: 11274207
references: Antioxid Redox Signal. 2009 Aug;11(8):1805-18
references: 19361273
references: Curr Alzheimer Res. 2004 Aug;1(3):175-81
references: 15975065
references: PLoS One. 2007 Jun 20;2(6):e536
references: 17579710
references: J Alzheimers Dis. 2004 Apr;6(2):171-5
references: 15096701
references: Mol Neurobiol. 2006 Apr;33(2):81-90
references: 16603790
references: J Alzheimers Dis. 2006 Jul;9(2):167-81
references: 16873964
references: FEBS Lett. 1994 Jul 25;349(1):109-16
references: 7913895
references: Science. 1996 Oct 4;274(5284):99-102
references: 8810256
references: J Neurochem. 1998 May;70(5):2212-5
references: 9572310
references: J Neurochem. 2004 Oct;91(2):423-8
references: 15447675
references: J Biol Chem. 2007 Apr 13;282(15):11590-601
references: 17308309
references: J Clin Invest. 2007 Jan;117(1):236-45
references: 17173140
references: Diabetes. 2004 Feb;53 Suppl 1:S130-5
references: 14749278
references: J Neurochem. 2002 Jan;80(1):91-100
references: 11796747
references: Science. 2006 Nov 3;314(5800):777-81
references: 17082447
references: Physiol Rev. 1997 Oct;77(4):1081-132
references: 9354812
references: Free Radic Biol Med. 2011 Jan 1;50(1):122-9
references: 21034809
references: J Cell Biol. 1998 Jun 15;141(6):1423-32
references: 9628898
references: Neurochem Int. 2009 Dec;55(7):662-70
references: 19560504
references: Arch Neurol. 2002 Sep;59(9):1381-9
references: 12223024
references: Neurobiol Aging. 1998 Jan-Feb;19(1):33-6
references: 9562500
references: Biochem J. 2003 Jun 15;372(Pt 3):757-66
references: 12646040
references: J Neurochem. 2008 Oct;107(1):197-207
references: 18680556
references: Lancet. 2005 Dec 17;366(9503):2112-7
references: 16360788
references: J Neurol Sci. 1996 Nov;143(1-2):137-42
references: 8981312
references: J Neurosci. 2001 Nov 1;21(21):8370-7
references: 11606625
references: J Biol Chem. 2011 Dec 30;286(52):44557-68
references: 22072713
references: J Alzheimers Dis. 1999 Oct;1(3):139-145
references: 12213999
references: Biochem J. 1999 Dec 1;344 Pt 2:461-7
references: 10567229
references: J Alzheimers Dis. 2006 Jul;9(2):147-53
references: 16873962
references: Neurobiol Aging. 2006 Aug;27(8):1094-9
references: 15993986
references: J Neuropathol Exp Neurol. 2001 Aug;60(8):759-67
references: 11487050
references: Neuron. 2007 Feb 1;53(3):337-51
references: 17270732
references: Neuroscience. 2002;115(1):201-11
references: 12401334
references: Front Biosci (Elite Ed). 2012 Jan 01;4:794-808
references: 22201914
references: J Alzheimers Dis. 2009;17(4):913-20
references: 19542619
references: Neurosci Lett. 2010 Jan 18;469(1):6-10
references: 19914330
references: J Neurochem. 2006 Mar;96(5):1322-35
references: 16478525
references: Appl Microbiol Biotechnol. 2004 May;64(4):465-72
references: 14740187
references: Neuroscience. 2001;104(3):609-13
references: 11440793
references: J Neurosci. 2008 Dec 31;28(53):14537-45
references: 19118188
references: Brain Res. 2007 Aug 3;1161:116-23
references: 17586478