title: A novel perspective on tau in Alzheimer's disease.
abstract: Mainstream thinking is dominated by the notion that the aggregation of specific proteins within neurons, and their subsequent formation into cytoplasmic and extracellular lesions, directly elicits neuronal dysfunction and death. Current dogma, for example, maintains that phosphorylated tau protein, the major component of neurofibrillary tangles, is a central mediator of disease pathogenesis. In this article, we challenge this classic notion by proposing that tau phosphorylation represents a compensatory response mounted by neurons against oxidative stress that serves a protective function. This concept provides a better understanding of the mechanisms underlying disease pathophysiology and also provides a window for therapeutic intervention.
authors: Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
authors: D J
authors: DJ
authors: Bonda
authors: R J
authors: RJ
authors: Castellani
authors: X
authors: X
authors: Zhu
authors: A
authors: A
authors: Nunomura
authors: H-g
authors: HG
authors: Lee
authors: G
authors: G
authors: Perry
authors: M A
authors: MA
authors: Smith
references: Brain Res Mol Brain Res. 2002 Dec 30;109(1-2):45-55
references: 12531514
references: J Neurochem. 2007 Jun;101(5):1172-84
references: 17286590
references: Am J Pathol. 2003 May;162(5):1623-7
references: 12707046
references: J Biol Chem. 1994 Aug 26;269(34):21614-9
references: 8063802
references: J Cell Biol. 1998 Nov 2;143(3):777-94
references: 9813097
references: Neurology. 1992 Mar;42(3 Pt 1):631-9
references: 1549228
references: Proc Natl Acad Sci U S A. 1995 Aug 29;92(18):8463-7
references: 7667312
references: J Neuropathol Exp Neurol. 2001 Aug;60(8):759-67
references: 11487050
references: J Neural Transm (Vienna). 2001;108(12):1397-415
references: 11810404
references: J Neurochem. 2001 Jan;76(2):435-41
references: 11208906
references: J Neurochem. 2004 Jun;89(5):1233-40
references: 15147516
references: Neurobiol Aging. 2002 Sep-Oct;23(5):855-9
references: 12392790
references: Curr Alzheimer Res. 2006 Sep;3(4):393-6
references: 17017869
references: J Biol Chem. 2002 Feb 15;277(7):4644-8
references: 11733539
references: Nature. 1994 Jun 9;369(6480):488-91
references: 8202139
references: J Neuropathol Exp Neurol. 2000 Oct;59(10):880-8
references: 11079778
references: J Neurosci. 1997 Apr 15;17(8):2653-7
references: 9092586
references: FEBS Lett. 2000 Dec 15;486(3):270-4
references: 11119717
references: Trends Neurosci. 2003 Feb;26(2):73-80
references: 12536130
references: Mech Ageing Dev. 2001 Dec;123(1):39-46
references: 11640950
references: Antioxid Redox Signal. 2003 Oct;5(5):571-6
references: 14580312
references: J Neural Transm Suppl. 1998;53:127-40
references: 9700651
references: J Neurochem. 2000 Sep;75(3):1234-41
references: 10936206
references: Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7787-91
references: 8052661
references: Brain Res Mol Brain Res. 2000 Dec 28;85(1-2):221-33
references: 11146125
references: Nat Rev Neurosci. 2007 Sep;8(9):663-72
references: 17684513
references: J Neurochem. 1999 May;72(5):2053-8
references: 10217284
references: J Cell Biol. 1998 Oct 5;143(1):171-81
references: 9763429
references: Lancet Neurol. 2004 Apr;3(4):219-26
references: 15039034
references: J Neuropathol Exp Neurol. 1999 Feb;58(2):188-97
references: 10029101
references: J Cell Biol. 1998 May 4;141(3):727-39
references: 9566972
references: J Biol Chem. 2001 Oct 12;276(41):37967-73
references: 11495914
references: Science. 1998 Nov 13;282(5392):1268-9
references: 9867630
references: J Cell Biol. 2002 Mar 18;156(6):1051-63
references: 11901170
references: J Neuropathol Exp Neurol. 2001 Dec;60(12):1190-7
references: 11764091
references: Cell Mol Life Sci. 2007 Sep;64(17):2219-33
references: 17604998
references: Brain Res. 1989 Jan 16;477(1-2):90-9
references: 2495152
references: J Neurosci. 1999 Mar 15;19(6):1959-64
references: 10066249
references: Proc Natl Acad Sci U S A. 1986 Jul;83(13):4913-7
references: 3088567
references: Am J Pathol. 1999 Dec;155(6):2153-65
references: 10595944
references: Science. 1998 Dec 4;282(5395):1914-7
references: 9836646
references: Science. 1991 Feb 22;251(4996):876-7
references: 1900373
references: Brain. 1964 Jun;87:307-20
references: 14188276
references: Free Radic Biol Med. 2002 Nov 1;33(9):1194-9
references: 12398927
references: Arch Neurol. 1973 Nov;29(5):324-7
references: 4743882
references: Science. 1987 Mar 27;235(4796):1641-4
references: 3029875
references: Time. 2001 Jan 15;157(2):80-1, 85
references: 11195696
references: Nat Med. 1996 Jul;2(7):783-7
references: 8673924
references: J Biol Chem. 1986 May 5;261(13):6084-9
references: 3084478
references: J Alzheimers Dis. 2001 Feb;3(1):41-48
references: 12214071
references: Acta Neuropathol. 2001 Apr;101(4):305-10
references: 11355301
references: Trends Mol Med. 2005 Apr;11(4):164-9
references: 15823754
references: J Neuropathol Exp Neurol. 1963 Oct;22:629-42
references: 14069842
references: FEBS Lett. 1998 Oct 23;437(3):207-10
references: 9824291
references: Am J Pathol. 2001 Jan;158(1):1-2
references: 11141471
references: Nature. 1963 Jan 12;197:192-3
references: 14032480
references: J Neuropathol Exp Neurol. 2000 Nov;59(11):1011-7
references: 11089579
references: Comp Biochem Physiol C Toxicol Pharmacol. 2002 Dec;133(4):507-13
references: 12458179
references: J Biol Chem. 2006 Sep 1;281(35):25457-65
references: 16803897