GLYCOGEN-SYNTHASE KINASE-3 INDUCES ALZHEIMERS DISEASE-LIKE PHOSPHORYLATION OF TAU - GENERATION OF PAIRED HELICAL FILAMENT EPITOPES AND NEURONAL LOCALIZATION OF THE KINASE

被引：658

作者：

HANGER, DP

HUGHES, K

WOODGETT, JR

BRION, JP

ANDERTON, BH

机构：

[1] LUDWIG INST CANC RES,LONDON,ENGLAND

[2] UNIV LIBRE BRUXELLES,ANAT PATHOL & MICROSCOPIE ELECTR LAB,B-1050 BRUSSELS,BELGIUM

来源：

NEUROSCIENCE LETTERS | 1992年 / 147卷 / 01期

基金：

英国惠康基金;

关键词：

TAU; ALZHEIMERS DISEASE; MICROTUBULE-ASSOCIATED PROTEIN; GLYCOGEN SYNTHASE KINASE-3; PROTEIN PHOSPHORYLATION; PROTEIN KINASE;

D O I：

10.1016/0304-3940(92)90774-2

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Glycogen synthase kinase-3 (GSK-3) reduced the mobility of human tau on SDS-PAGE, prevented binding of the monoclonal antibody (mAb). Tau.l, and induced binding of the mAb 8D8. Recombinant tau phosphorylated by GSK-3 aligned on SDS-PAGE with the abnormally phosphorylated tau (PHF-tau) associated with the paired helical filaments in Alzheimer's disease brain. Phosphorylated serine396 (numbering of the largest human brain tau isoform) was identified as a binding site on tau for mAb 8D8. The localisation of GSK-3 within granular structures in pyramidal cells indicates that GSK-3alpha and GSK-3beta may have a role in the production of PHF-tau in Alzheimer's disease.

引用

页码：58 / 62

页数：5