Tau as a Therapeutic Target for Alzheimer's Disease

被引:66
|
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
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
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