The Emerging Link between O-GlcNAc and Alzheimer Disease

被引：200
|
作者：
Zhu, Yanping [1 ,2 ]
Shan, Xiaoyang [1 ]
Yuzwa, Scott A. [1 ]
Vocadlo, David J. [1 ,2 ]
机构：
[1] Simon Fraser Univ, Dept Mol Biol & Biochem, Burnaby, BC V5A 1S6, Canada
[2] Simon Fraser Univ, Dept Chem, Burnaby, BC V5A 1S6, Canada
来源：
JOURNAL OF BIOLOGICAL CHEMISTRY | 2014年 / 289卷 / 50期
基金：
加拿大自然科学与工程研究理事会; 加拿大健康研究院;
关键词：
Alzheimer Disease; Amyloid- (A); Brain Metabolism; Glucose Metabolism; Glycobiology; Glycoprotein; Glycosylation; O-GlcNAcylation; O-Linked N-Acetylglucosamine (O-GlcNAc); Tau Protein (Tau); AMYLOID PRECURSOR PROTEIN; PAIRED HELICAL FILAMENTS; TAU TRANSGENIC MICE; BETA-N-ACETYLGLUCOSAMINIDASE; GLUCOSE-METABOLISM; INSULIN-RESISTANCE; MASS-SPECTROMETRY; COGNITIVE DECLINE; MOUSE MODEL; NUCLEOCYTOPLASMIC PROTEINS;
D O I：
10.1074/jbc.R114.601351
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Regional glucose hypometabolism is a defining feature of Alzheimer disease (AD). One emerging link between glucose hypometabolism and progression of AD is the nutrient-responsive post-translational O-GlcNAcylation of nucleocytoplasmic proteins. O-GlcNAc is abundant in neurons and occurs on both tau and amyloid precursor protein. Increased brain O-GlcNAcylation protects against tau and amyloid- peptide toxicity. Decreased O-GlcNAcylation occurs in AD, suggesting that glucose hypometabolism may impair the protective roles of O-GlcNAc within neurons and enable neurodegeneration. Here, we review how O-GlcNAc may link cerebral glucose hypometabolism to progression of AD and summarize data regarding the protective role of O-GlcNAc in AD models.
引用
收藏
页码：34472 / 34481
页数：10
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