在阿尔茨海默氏症患者中,人类大脑的葡萄糖形式协同调节网络和葡萄糖素修饰变化在阿尔茨海默氏症中发生变化
Qi Zhang1, Cheng Ma2, Lih-Shen Chin1
1Department of Pharmacology and Chemical Biology, Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA 30322, USA.
Science advances
|April 5, 2024
概括
阿尔茨海默病 (AD) 改变了大脑蛋白质的糖化,影响健康. 这项研究绘制了超过10,000个N-glycoforms的地图,揭示了与AD病理学相关的化,化和分支的关键变化.
科学领域:
- 神经科学是一个神经科学.
- 生物化学 生物化学
- 系统生物学 系统生物学
背景情况:
- 蛋白质糖化对大脑功能至关重要.
- 对人类大脑的葡萄糖形式及其在阿尔茨海默病 (AD) 中的作用的理解有限.
研究的目的:
- 为了执行人类AD和对照大脑的蛋白质组全方位糖形概况.
- 为了识别大脑糖形和糖修饰的疾病特异性变化.
- 探索大脑糖蛋白质组的组织原理及其与AD病理学的关联.
主要方法:
- 基于完整的葡萄糖的定量葡萄糖保护组学.
- 系统生物学方法用于网络和模块分析.
- 对阿尔茨海默病患者和对照人群死后人类大脑组织的分析.
主要成果:
- 鉴定了人类大脑中近1200种葡萄糖蛋白中的1万多种N-葡萄糖形式.
- 发现了与AD相关的糖形特征:降低了化/分支,增加了曼诺化/截断.
- 发现了与AD临床表型,粉样β和tau病理学相关的糖形/糖甘模块.
结论:
- 提供了全面的洞察力,大脑葡萄糖蛋白质组改变在AD.
- 突出了糖基化变化的潜力,作为AD的生物标志物和治疗点.
- 为未来的AD研究和基于糖化基的干预建立了宝贵的资源.
相关概念视频
Alzheimer's Disease: Overview
469
Alzheimer's Disease (AD) is a continually advancing neurodegenerative disorder, distinguished by escalating memory loss, cognitive dysfunction, and dementia. The disease unfolds in three stages: preclinical, mild cognitive impairment (MCI), and dementia. Its onset is insidious, and the progression gradual, with the cause not well explained by other disorders.
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ...
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ...
469
Protein Glycosylation
6.9K
Glycosylation, the most common post-translational modification for proteins, serves diverse functions. Adding sugars to proteins makes the proteins more resistant to proteolytic digestion. Glycosylated proteins can act as markers and receptors to promote cell-cell adhesion. Additionally, they have many essential quality control functions in the cell, such as correct protein folding and facilitating transport of misfolded proteins to the cytosol, which can be degraded.
Glycosylation occurs in...
Glycosylation occurs in...
6.9K
Proteoglycans
3.9K
Glycans, a class of complex heterogeneous molecules, can be covalently attached to proteins to form glycosylated proteins that regulate various physiological and pathological processes. Glycosylated proteins or glycoproteins comprise N-linked and O-linked oligosaccharides. O-glycosylation is the most common type of protein glycosylation. Here, glycans attach to the oxygen atom of the hydroxyl groups of Serine or Threonine residues. O-linked glycosylation occurs later in protein processing,...
3.9K
Oligosaccharide Assembly
2.8K
Protein glycosylation starts in the ER lumen and continues in the Golgi apparatus. Glycosyltransferases catalyze the addition of sugar molecules or glycosylation of proteins. Usually, these enzymes add sugars to the hydroxyl groups of selected serine or threonine residues to form O-linked glycans or the amino groups of asparagine residues to form N-linked glycans. Different positions on the same polypeptide chain can contain differently linked glycans.
Multiple sugar molecules that may or may...
Multiple sugar molecules that may or may...
2.8K
Amyloid Fibrils
9.5K
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
9.5K
Neural Regulation
39.4K
Digestion begins with a cephalic phase that prepares the digestive system to receive food. When our brain processes visual or olfactory information about food, it triggers impulses in the cranial nerves innervating the salivary glands and stomach to prepare for food.
39.4K


