title: Tau clearance mechanisms and their possible role in the pathogenesis of Alzheimer disease.
abstract: One of the defining pathological features of Alzheimer disease (AD) is the intraneuronal accumulation of tau. The tau that forms these accumulations is altered both posttranslationally and conformationally, and there is now significant evidence that soluble forms of these modified tau species are the toxic entities rather than the insoluble neurofibrillary tangles. However there is still noteworthy debate concerning which specific pathological forms of tau are the contributors to neuronal dysfunction and death in AD. Given that increases in aberrant forms of tau play a role in the neurodegeneration process in AD, there is growing interest in understanding the degradative pathways that remove tau from the cell, and the selectivity of these different pathways for various forms of tau. Indeed, one can speculate that deficits in a pathway that selectively removes certain pathological forms of tau could play a pivotal role in AD. In this review we will discuss the different proteolytic and degradative machineries that may be involved in removing tau from the cell. How deficits in these different degradative pathways may contribute to abnormal accumulation of tau in AD will also be considered. In addition, the issue of the selective targeting of specific tau species to a given degradative pathway for clearance from the cell will be addressed.
authors.affiliation: Neuroscience Graduate Program, Department of Anesthesiology, University of Rochester , Rochester, NY , USA.
authors.forename: Adrianne S
authors.initials: AS
authors.lastname: Chesser
authors.forename: Susanne M
authors.initials: SM
authors.lastname: Pritchard
authors.forename: Gail V W
authors.initials: GV
authors.lastname: Johnson
keywords: autophagy; degradation; proteasome; proteolysis; tau
references.citation: Hum Mol Genet. 2008 Aug 15;17(16):2570-82
references.pmid: 18502787
references.citation: Neuron. 1993 Jun;10(6):1151-60
references.pmid: 8391280
references.citation: J Biol Chem. 2003 Sep 26;278(39):37681-9
references.pmid: 12821672
references.citation: J Neurobiol. 1998 Jul;36(1):64-80
references.pmid: 9658339
references.citation: Acta Neuropathol. 2012 Jan;123(1):53-70
references.pmid: 22020633
references.citation: J Neurochem. 1996 Nov;67(5):1846-55
references.pmid: 8863489
references.citation: J Neurochem. 2002 Oct;83(1):176-85
references.pmid: 12358741
references.citation: Arch Neurol. 2003 May;60(5):729-36
references.pmid: 12756137
references.citation: J Neurosci. 1998 Sep 15;18(18):7061-74
references.pmid: 9736630
references.citation: FASEB J. 2006 Apr;20(6):753-5
references.pmid: 16464956
references.citation: J Biol Chem. 2011 Jun 10;286(23):20797-811
references.pmid: 21482827
references.citation: J Neurosci. 2011 Jan 12;31(2):700-11
references.pmid: 21228179
references.citation: Nat Immunol. 2009 Nov;10(11):1137-9
references.pmid: 19841643
references.citation: Biochemistry. 2007 Jun 26;46(25):7325-36
references.pmid: 17542619
references.citation: J Biol Chem. 2010 Jul 16;285(29):21978-87
references.pmid: 20466727
references.citation: J Neuropathol Exp Neurol. 2003 May;62(5):451-63
references.pmid: 12769185
references.citation: Biochem Soc Trans. 2012 Aug;40(4):667-71
references.pmid: 22817713
references.citation: Mol Cell Biol. 2009 Aug;29(15):4177-87
references.pmid: 19470753
references.citation: Acta Neuropathol. 1991;82(4):239-59
references.pmid: 1759558
references.citation: Arch Neurol. 1997 Oct;54(10):1234-40
references.pmid: 9341569
references.citation: J Cell Biol. 1988 May;106(5):1583-91
references.pmid: 3131347
references.citation: J Cell Biochem. 2009 May 15;107(2):253-63
references.pmid: 19301262
references.citation: Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10252-7
references.pmid: 17535890
references.citation: J Neurosci. 1998 Sep 1;18(17):6882-91
references.pmid: 9712658
references.citation: Proc Natl Acad Sci U S A. 2003 Aug 19;100(17):10032-7
references.pmid: 12888622
references.citation: J Neuropathol Exp Neurol. 2005 Feb;64(2):113-22
references.pmid: 15751225
references.citation: PLoS One. 2011;6(8):e23865
references.pmid: 21858230
references.citation: Cell. 2012 Mar 30;149(1):232-44
references.pmid: 22464332
references.citation: Biochem Biophys Res Commun. 1996 Feb 15;219(2):591-7
references.pmid: 8605032
references.citation: FEBS Lett. 2010 Apr 2;584(7):1393-8
references.pmid: 20040365
references.citation: J Biol Chem. 2006 Apr 21;281(16):10825-38
references.pmid: 16443603
references.citation: J Neurochem. 1991 Nov;57(5):1577-83
references.pmid: 1919574
references.citation: J Neurochem. 2000 Aug;75(2):624-33
references.pmid: 10899937
references.citation: Prog Neurobiol. 2013 Jun;105:49-59
references.pmid: 23528736
references.citation: Neurobiol Aging. 2005 Jul;26(7):1015-22
references.pmid: 15748781
references.citation: Aging Cell. 2013 Jun;12(3):370-80
references.pmid: 23425014
references.citation: Exp Neurol. 1999 Aug;158(2):312-27
references.pmid: 10415139
references.citation: Neurobiol Dis. 2011 Jul;43(1):38-45
references.pmid: 21296668
references.citation: J Neurochem. 2000 Jul;75(1):436-9
references.pmid: 10854289
references.citation: J Neuropathol Exp Neurol. 2008 May;67(5):470-83
references.pmid: 18431250
references.citation: Cell Death Dis. 2012 Jun 21;3:e326
references.pmid: 22717581
references.citation: J Neurosci Res. 1998 Jul 15;53(2):153-64
references.pmid: 9671972
references.citation: J Neurochem. 2005 Jul;94(1):192-203
references.pmid: 15953362
references.citation: Nat Rev Mol Cell Biol. 2011 Mar;12(3):152-62
references.pmid: 21326199
references.citation: FASEB J. 2012 May;26(5):1946-59
references.pmid: 22253473
references.citation: Brain Res. 1998 Jun 29;797(2):321-7
references.pmid: 9666159
references.citation: Mol Neurobiol. 2005;31(1-3):3-16
references.pmid: 15953808
references.citation: Mol Neurodegener. 2010 Nov 05;5:48
references.pmid: 21054848
references.citation: Arch Biochem Biophys. 2010 Aug 15;500(2):181-8
references.pmid: 20478262
references.citation: J Histochem Cytochem. 2003 Oct;51(10):1279-84
references.pmid: 14500695
references.citation: J Neural Transm (Vienna). 2005 Apr;112(4):547-55
references.pmid: 15372326
references.citation: Cold Spring Harb Perspect Biol. 2012 Oct 01;4(10):
references.pmid: 22983160
references.citation: Mol Neurobiol. 2008 Aug;38(1):78-100
references.pmid: 18686046
references.citation: Hum Mol Genet. 2011 May 1;20(9):1820-33
references.pmid: 21320871
references.citation: Autophagy. 2007 Jul-Aug;3(4):295-9
references.pmid: 17404494
references.citation: Mol Cell. 2012 Nov 9;48(3):329-42
references.pmid: 23022382
references.citation: J Neurochem. 2009 Jul;110(1):328-42
references.pmid: 19457109
references.citation: Hum Mol Genet. 2004 Apr 1;13(7):703-14
references.pmid: 14962978
references.citation: Cell. 2012 Aug 17;150(4):803-15
references.pmid: 22901810
references.citation: Hum Mol Genet. 2010 Dec 1;19(23):4573-86
references.pmid: 20829225
references.citation: J Clin Invest. 2008 May;118(5):1877-89
references.pmid: 18431510
references.citation: Am J Pathol. 2008 Sep;173(3):665-81
references.pmid: 18688038
references.citation: J Clin Invest. 2004 Jul;114(1):121-30
references.pmid: 15232619
references.citation: Brain. 2012 Jul;135(Pt 7):2169-77
references.pmid: 22689910
references.citation: J Biol Chem. 2007 Aug 17;282(33):24131-45
references.pmid: 17580304
references.citation: Mol Med. 2011;17(7-8):676-85
references.pmid: 21442128
references.citation: Sci Signal. 2008 Apr 08;1(14):re1
references.pmid: 18398107
references.citation: Am J Pathol. 2004 Aug;165(2):523-31
references.pmid: 15277226
references.citation: Neurobiol Dis. 2001 Feb;8(1):162-72
references.pmid: 11162250
references.citation: Neurobiol Aging. 2012 Oct;33(10):2291-305
references.pmid: 22169203
references.citation: FEBS Lett. 2011 Nov 4;585(21):3424-9
references.pmid: 21983102
references.citation: Mol Neurodegener. 2012 Sep 21;7:48
references.pmid: 22998728
references.citation: Am J Pathol. 2010 Apr;176(4):1600-6
references.pmid: 20150433
references.citation: Eur J Neurosci. 2008 Mar;27(5):1119-30
references.pmid: 18294209
references.citation: Autophagy. 2012 Apr;8(4):609-22
references.pmid: 22361619
references.citation: PLoS Genet. 2010 Jul 15;6(7):e1001026
references.pmid: 20664788
references.citation: J Neurosci. 2004 Sep 8;24(36):7895-902
references.pmid: 15356202
references.citation: Biochemistry. 2006 Dec 19;45(50):15111-9
references.pmid: 17154549
references.citation: J Neurochem. 2003 Apr;85(1):115-22
references.pmid: 12641733
references.citation: J Neurosci Res. 1998 Jun 15;52(6):691-8
references.pmid: 9669318
references.citation: Acta Neuropathol. 2002 Jul;104(1):92-104
references.pmid: 12070670
references.citation: Proc Natl Acad Sci U S A. 2005 Apr 26;102(17):6021-6
references.pmid: 15855271
references.citation: J Neurosci. 2005 Jun 1;25(22):5365-75
references.pmid: 15930385
references.citation: Neurobiol Dis. 2001 Feb;8(1):19-31
references.pmid: 11162237
references.citation: Nat Commun. 2011;2:252
references.pmid: 21427723
references.citation: Neurobiol Aging. 2008 Nov;29(11):1607-18
references.pmid: 17544172
references.citation: J Neurosci. 2012 Feb 1;32(5):1847-58
references.pmid: 22302823
references.citation: Cell. 2010 Aug 6;142(3):387-97
references.pmid: 20655099
references.citation: Neuron. 2006 Sep 7;51(5):549-60
references.pmid: 16950154
references.citation: Brain. 2011 Jan;134(Pt 1):258-77
references.pmid: 21186265
references.citation: J Biol Chem. 2005 Feb 18;280(7):5145-53
references.pmid: 15542598
references.citation: J Neurochem. 2000 Apr;74(4):1469-77
references.pmid: 10737603
references.citation: J Biol Chem. 1996 Nov 15;271(46):28741-4
references.pmid: 8910513
references.citation: Hum Mol Genet. 2009 Nov 1;18(21):4153-70
references.pmid: 19654187
references.citation: ASN Neuro. 2011 Feb 16;3(1):e00051
references.pmid: 21359008
references.citation: Neurobiol Aging. 2011 Jan;32(1):1-14
references.pmid: 20961659
references.citation: Physiol Rev. 2010 Oct;90(4):1383-435
references.pmid: 20959619
references.citation: FEBS Lett. 2010 Jun 18;584(12):2635-45
references.pmid: 20412801
references.citation: J Biol Chem. 2012 Jun 15;287(25):20931-41
references.pmid: 22535953
references.citation: J Biol Chem. 2006 Jan 13;281(2):1205-14
references.pmid: 16246844
references.citation: Autophagy. 2011 Mar;7(3):279-96
references.pmid: 21189453
references.citation: Biochem Biophys Res Commun. 1994 Jun 15;201(2):716-21
references.pmid: 8003007
references.citation: Nat Genet. 2000 Aug;25(4):402-5
references.pmid: 10932182
references.citation: Int J Clin Exp Pathol. 2009 Jun 15;2(6):561-73
references.pmid: 19636403
references.citation: J Neuropathol Exp Neurol. 2006 Jan;65(1):19-25
references.pmid: 16410745
references.citation: J Neuropathol Exp Neurol. 2005 Feb;64(2):104-12
references.pmid: 15751224
references.citation: Nature. 2010 Apr 22;464(7292):1201-4
references.pmid: 20357768
references.citation: Brain Res. 2001 Apr 20;898(2):350-7
references.pmid: 11306022