The role of tau kinases in Alzheimer's disease.
A principal feature of the progression of Alzheimer's disease (AD) is the appearance of aberrant phosphorylation of the microtubule-associated protein tau in the brains of affected individuals. Significant research efforts have been directed at identifying the kinases involved in this process, as well as developing pharmacological agents to inhibit these molecules. This review focuses on recent developments in both the physiological and pathological effects of tau phosphorylation, and the contribution of phosphorylation to tau toxicity and pathological progression in AD. The evolving concepts of the roles tau plays in cellular biology, and the mechanisms by which phosphorylation regulates tau function, is reshaping the framework for the development of therapeutics targeting tau to treat AD.
Dolan
Philip J
PJ
University of Alabama at Birmingham, Department of Cell Biology, 1530 3rd Avenue South, Birmingham, AL 35294, USA.
Johnson
Gail V W
GV
D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D018450:Disease Progression; D006801:Humans; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D011494:Protein Kinases / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism / Q000502:physiology*
D016229:Amyloid beta-Peptides; D047428:Protein Kinase Inhibitors; D016875:tau Proteins; D011494:Protein Kinases
Acta Neuropathol. 1991;82(4):239-59
1759558
Neurobiol Dis. 2004 Nov;17(2):326-36
15474370
J Neurosci. 2002 Jan 1;22(1):10-20
11756483
J Neurosci. 2007 Dec 12;27(50):13635-48
18077675
J Neurochem. 1994 Jan;62(1):372-5
8263540
J Alzheimers Dis. 2002 Oct;4(5):417-30
12446973
J Neurosci. 2009 May 6;29(18):5758-67
19420244
J Biol Chem. 1984 Apr 25;259(8):5301-5
6425287
Cell Signal. 2009 Feb;21(2):264-73
19007880
J Neurosci. 1992 Feb;12(2):376-89
1346802
Biochemistry. 1999 Mar 23;38(12):3549-58
10090741
J Neurosci. 2005 Jul 13;25(28):6584-93
16014719
Nat Chem Biol. 2008 Aug;4(8):483-90
18587388
J Neurosci Res. 2009 Feb;87(2):440-51
18798283
Curr Alzheimer Res. 2005 Jan;2(1):3-18
15977985
Nature. 1980 Mar 27;284(5754):353-5
7360270
Science. 2005 Jul 15;309(5733):476-81
16020737
Science. 2002 Dec 6;298(5600):1912-34
12471243
Proc Natl Acad Sci U S A. 1986 Jun;83(11):4040-3
2424015
Curr Alzheimer Res. 2004 Feb;1(1):47-54
15975085
Proc Natl Acad Sci U S A. 2009 Oct 27;106(43):18367-72
19837693
Science. 2005 Feb 25;307(5713):1282-8
15731448
Behav Genet. 1978 Jul;8(4):315-31
567976
Cell. 1997 Apr 18;89(2):297-308
9108484
Proc Natl Acad Sci U S A. 2008 Oct 14;105(41):15997-6002
18832465
J Neurosci. 2010 Apr 7;30(14):4845-56
20371804
Curr Alzheimer Res. 2008 Dec;5(6):591-8
19075586
J Neurosci. 2003 Nov 19;23(33):10633-44
14627648
Neurobiol Aging. 2011 Jul;32(7):1249-61
19700222
FEBS Lett. 1999 Jun 25;453(3):260-4
10405156
Toxicol Pathol. 2008 Jun;36(4):529-51
18467681
J Neurosci. 2007 Mar 14;27(11):2896-907
17360912
J Alzheimers Dis. 2008 Aug;14(4):365-70
18688085
Biochem J. 1994 Aug 1;301 ( Pt 3):871-7
7519852
J Neurosci. 2002 Nov 1;22(21):9340-51
12417659
Mol Biol Cell. 2008 Jul;19(7):3052-69
18480410
Hum Mol Genet. 2009 Jan 1;18(1):164-77
18930955
J Neurochem. 1998 Apr;70(4):1346-56
9523550
J Neurosci Res. 2007 Sep;85(12):2620-30
17265463
Nature. 2000 May 18;405(6784):360-4
10830966
Nature. 2004 Oct 14;431(7010):805-10
15483602
Science. 2001 Aug 24;293(5534):1487-91
11520987
Eur J Neurosci. 2008 Nov;28(10):1989-2002
19046381
Acta Neuropathol. 2009 Jul;118(1):53-69
19184068
J Neurosci. 2008 Dec 31;28(53):14511-21
19118186
Science. 1991 Feb 8;251(4994):675-8
1899488
Mol Cell Neurosci. 1997;9(3):220-34
9245504
J Neurosci. 2006 Mar 8;26(10):2738-44
16525053
J Neurochem. 2010 May;113(4):895-903
20193038
Mol Cell. 2008 Sep 26;31(6):873-85
18922469
Bioessays. 2008 Jan;30(1):10-4
18081006
Aging Cell. 2010 Feb;9(1):64-77
19895631
EMBO J. 1992 Apr;11(4):1593-7
1563356
Biochemistry. 2009 Oct 27;48(42):10047-55
19769346
J Biol Chem. 1995 Aug 11;270(32):18917-22
7642549
J Cell Sci. 1996 Jun;109 ( Pt 6):1537-43
8799840
FASEB J. 2010 Aug;24(8):2904-15
20354135
FASEB J. 2008 Sep;22(9):3186-95
18511549
J Neurosci. 2006 Oct 4;26(40):10129-40
17021169
J Neurosci. 2007 Aug 22;27(34):9115-29
17715348
Proc Natl Acad Sci U S A. 2009 Dec 8;106(49):20936-41
19926863
J Neurosci. 2007 Mar 21;27(12):3090-7
17376970
Biochim Biophys Acta. 2005 Jan 3;1739(2-3):280-97
15615646
J Biol Chem. 1997 Aug 1;272(31):19547-53
9235959
J Cell Sci. 2005 Oct 15;118(Pt 20):4645-54
16176937
Neuron. 1996 Dec;17(6):1201-7
8982166
J Cell Sci. 1998 Nov;111 ( Pt 21):3167-77
9763511
Proc Natl Acad Sci U S A. 1986 Jun;83(11):4044-8
2424016
J Neural Transm Suppl. 2007;(72):217-33
17982898
Proc Natl Acad Sci U S A. 1986 Jul;83(13):4913-7
3088567
Am J Pathol. 2009 Nov;175(5):2089-98
19815707
Neurobiol Aging. 2011 Jun;32(6):991-1006
19660835
Neuron. 1989 Oct;3(4):519-26
2484340
Mol Psychiatry. 2003 Apr;8(4):413-22, 363
12740599
J Biol Chem. 2007 Apr 13;282(15):11590-601
17308309
Neuroscience. 2010 Jun 30;168(2):323-34
20394726
Neuroscience. 2010 Jun 2;167(4):1044-56
20211702
EMBO J. 2002 Feb 1;21(3):281-93
11823421
PLoS One. 2009 Nov 19;4(11):e7917
19936237
Neuron. 2000 Nov;28(2):449-59
11144355
Neuron. 1995 Apr;14(4):879-88
7718249
Science. 2007 May 4;316(5825):750-4
17478722
Biochemistry. 2004 Jun 8;43(22):6899-908
15170327
Proc Natl Acad Sci U S A. 1975 May;72(5):1858-62
1057175
Science. 1986 May 2;232(4750):648-50
3083509
Diabetes. 2006 Dec;55(12):3320-5
17130475
Nat Genet. 2007 Dec;39(12):1434-6
18037885
J Alzheimers Dis. 2010;19(2):721-33
20110615
J Biol Chem. 2009 Jul 31;284(31):20909-16
19491104
Biochim Biophys Acta. 2003 Jan 20;1619(2):167-76
12527113
Biochem Biophys Res Commun. 2007 Jun 29;358(2):644-9
17499212
J Neurosci. 2009 Jul 15;29(28):9078-89
19605645
Glia. 2005 May;50(3):235-46
15739188
J Neurochem. 2007 May;101(3):757-70
17448147
Biol Psychiatry. 2000 Oct 15;48(8):740-54
11063971
Mol Biol Cell. 1995 Dec;6(12):1887-902
8590813
J Neurosci Res. 1994 Dec 15;39(6):669-73
7534834
Annu Rev Neurosci. 2008;31:151-73
18558852
Eur J Biochem. 1978 Apr;85(1):43-53
639823
Neuron. 2003 Jul 31;39(3):409-21
12895417
Biochemistry. 1992 Nov 3;31(43):10626-33
1420178
Nat Genet. 2000 Aug;25(4):402-5
10932182
FEBS Lett. 2004 May 21;566(1-3):261-9
15147906
Free Radic Biol Med. 2003 Jul 1;35(1):45-58
12826255
Dement Geriatr Cogn Disord. 2007;24(4):247-52
17700020
Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):13287-92
9371838
Nature. 2010 Apr 22;464(7292):1201-4
20357768
Exp Neurol. 2003 Apr;180(2):144-55
12684028