Role of glycosylation in hyperphosphorylation of tau in Alzheimer's disease

FEBS Letters

Merkle, Roberta K.¹  Zaidi, Tanweer²  Gong, Cheng-Xin²  Liu, Fei²  Grundke-Iqbal, Inge²  Iqbal, Khalid² 

[1]Complex Carbohydrate Research Center, the University of Georgia, 220 Riverbend Road, Athens, GA 30602, USA

[2]Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314, USA

关键词: Tau;    Glycosylation;    Phosphorylation;    Alzheimer's disease;    Neurofibrillary degeneration;    Lectin;    AD;    Alzheimer's disease;    AD-tau;    AD non-hyperphosphorylated tau;    AD P-tau;    AD abnormally phosphorylated tau;    B-tau;    bovine tau;    GalNAc;    N-acetyl-D-galactosamine;    GlcNAc;    N-acetyl-D-glucosamine;    N-tau;    normal human tau;    PHF;    paired helical filaments;    PKA;    cAMP-dependent protein kinase;    PNGase F;    peptide-N-glycosidase F;   

DOI  :  10.1016/S0014-5793(02)02228-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

In Alzheimer's disease (AD) brain, microtubule-associated protein tau is abnormally modified by hyperphosphorylation and glycosylation, and is aggregated as neurofibrillary tangles of paired helical filaments. To investigate the role of tau glycosylation in neurofibrillary pathology, we isolated various pools of tau protein from AD brain which represent different stages of tau pathology. We found that the non-hyperphosphorylated tau from AD brain but not normal brain tau was glycosylated. Monosaccharide composition analyses and specific lectin blots suggested that the tau in AD brain was glycosylated mainly through N-linkage. In vitro phosphorylation indicated that the glycosylated tau was a better substrate for cAMP-dependent protein kinase than the deglycosylated tau. These results suggest that the glycosylation of tau is an early abnormality that can facilitate the subsequent abnormal hyperphosphorylation of tau in AD brain.

【 授权许可】

Unknown