Tau as a Therapeutic Target for Alzheimer's Disease

被引:81
作者
Boutajangout, A. [1 ,2 ,3 ]
Sigurdsson, E. M. [1 ,2 ,3 ]
Krishnamurthy, P. K. [1 ,2 ]
机构
[1] NYU, Sch Med, Dept Physiol, New York, NY 10016 USA
[2] NYU, Sch Med, Dept Neurosci, New York, NY 10016 USA
[3] NYU, Sch Med, Dept Psychiat, New York, NY 10016 USA
关键词
Tau; therapy; kinases; phosphatase; aggregation; immunotherapy; GLYCOGEN-SYNTHASE KINASE-3; CYCLIN-DEPENDENT KINASE-5; PAIRED-HELICAL FILAMENTS; AFFINITY-REGULATING KINASE; MICROTUBULE-ASSOCIATED PROTEINS; ABNORMALLY PHOSPHORYLATED-TAU; SMALL-MOLECULE INHIBITORS; TRANSGENIC MOUSE MODEL; PROLYL ISOMERASE PIN1; AMYLOID-BETA-PEPTIDE;
D O I
10.2174/156720511796717195
中图分类号
R74 [神经病学与精神病学];
学科分类号
100204 [神经病学];
摘要
Neurofibrillary tangles (NFTs) are one of the pathological hallmarks of Alzheimer's disease (AD) and are primarily composed of aggregates of hyperphosphorylated forms of the microtubule associated protein tau. It is likely that an imbalance of kinase and phosphatase activities leads to the abnormal phosphorylation of tau and subsequent aggregation. The wide ranging therapeutic approaches that are being developed include to inhibit tau kinases, to enhance phosphatase activity, to promote microtubule stability, and to reduce tau aggregate formation and/or enhance their clearance with small molecule drugs or by immunotherapeutic means. Most of these promising approaches are still in preclinical development whilst some have progressed to Phase II clinical trials. By pursuing these lines of study, a viable therapy for AD and related tauopathies may be obtained.
引用
收藏
页码:666 / 677
页数:12
相关论文
共 222 条
[1]
Hyperphosphorylated tan and neurofilament and cytoskeletal disruptions in mice overexpressing human p25, an activator of cdk5 [J].
Ahlijanian, MK ;
Barrezueta, NX ;
Williams, RD ;
Jakowski, A ;
Kowsz, KP ;
McCarthy, S ;
Coskran, T ;
Carlo, A ;
Seymour, PA ;
Burkhardt, JE ;
Nelson, RB ;
McNeish, JD .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (06) :2910-2915
[2]
Regulation of tau phosphorylation and protection against β-amyloid-induced neurodegeneration by lithium.: Possible implications for Alzheimer's disease [J].
Alvarez, G ;
Muñoz-Montaño, JR ;
Satrústegui, J ;
Avila, J ;
Bogónez, E ;
Díaz-Nido, J .
BIPOLAR DISORDERS, 2002, 4 (03) :153-165
[3]
Anderton BH, 2001, BIOCHEM SOC SYMP, V67, P73
[4]
NEUROFIBRILLARY TANGLES BUT NOT SENILE PLAQUES PARALLEL DURATION AND SEVERITY OF ALZHEIMERS-DISEASE [J].
ARRIAGADA, PV ;
GROWDON, JH ;
HEDLEYWHYTE, ET ;
HYMAN, BT .
NEUROLOGY, 1992, 42 (03) :631-639
[5]
Immunotherapy targeting pathological tau conformers in a tangle mouse model reduces brain pathology with associated functional improvements [J].
Asuni, Ayodeji A. ;
Boutajangout, Allal ;
Quartermain, David ;
Sigurdsson, Einar M. .
JOURNAL OF NEUROSCIENCE, 2007, 27 (34) :9115-9129
[6]
Specific tau phosphorylation sites correlate with severity of neuronal cytopathology in Alzheimer's disease [J].
Augustinack, JC ;
Schneider, A ;
Mandelkow, EM ;
Hyman, BT .
ACTA NEUROPATHOLOGICA, 2002, 103 (01) :26-35
[7]
Barakos J, 2010, LANCET NEUROL
[8]
Peripherally administered antibodies against amyloid β-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease [J].
Bard, F ;
Cannon, C ;
Barbour, R ;
Burke, RL ;
Games, D ;
Grajeda, H ;
Guido, T ;
Hu, K ;
Huang, JP ;
Johnson-Wood, K ;
Khan, K ;
Kholodenko, D ;
Lee, M ;
Lieberburg, I ;
Motter, R ;
Nguyen, M ;
Soriano, F ;
Vasquez, N ;
Weiss, K ;
Welch, B ;
Seubert, P ;
Schenk, D ;
Yednock, T .
NATURE MEDICINE, 2000, 6 (08) :916-919
[9]
Complete sequence of a novel protein containing a femtomolar-activity-dependent neuroprotective peptide [J].
Bassan, M ;
Zamostiano, R ;
Davidson, A ;
Pinhasov, A ;
Giladi, E ;
Perl, O ;
Bassan, H ;
Blat, C ;
Gibney, G ;
Glazner, G ;
Brenneman, DE ;
Gozes, I .
JOURNAL OF NEUROCHEMISTRY, 1999, 72 (03) :1283-1293
[10]
Bauer B, 2005, EXP BIOL MED, V230, P118