Proteomics

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Multilayered N-glycoproteome Profiling Reveals Highly Heterogeneous and Dysregulated Protein N-glycosylations Related to Alzheimer’s Disease


ABSTRACT: Protein N-glycosylation is ubiquitous in brain and closely related to cognition and memory. Alzheimer's disease (AD) is a multifactorial disorder that lacks clear pathogenesis and treatment. Aberrant N-glycosylation has been suggested to be involved in AD pathology. While the systematic variations of protein N-glycosylation and their roles in AD have not been thoroughly investigated due to technically challenging. Here, we applied multilayered N-glycoproteomics to quantify the global protein expression, N-glycosylation sites, N-glycans, and site-specific N-glycopeptides in AD mice brains (APP/PS1 transgenic) versus wild type. The N-glycoproteome landscape exhibited the highly complex site-specific heterogeneity in AD brains. Quantitative analyses explored the generally dysregulated N-glycosylations in AD, involving proteins such as glutamate receptors, as well as fucosylated and oligo-mannose glycans. Furthermore, functional study revealed the crucial roles of N-glycosylation on proteins and neuron cells. Our work provided a robust multilayered N-glycoproteomics workflow for AD and can be applied to widespread biological systems.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Pan Fang  

LAB HEAD: Huli Shen

PROVIDER: PXD015335 | Pride | 2019-11-25

REPOSITORIES: Pride

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Multilayered N-Glycoproteome Profiling Reveals Highly Heterogeneous and Dysregulated Protein N-Glycosylation Related to Alzheimer's Disease.

Fang Pan P   Xie JuanJuan J   Sang Shaoming S   Zhang Lei L   Liu Mingqi M   Yang Lujie L   Xu Yiteng Y   Yan Guoquan G   Yao Jun J   Gao Xing X   Qian Wenjing W   Wang Zhongfeng Z   Zhang Yang Y   Yang Pengyuan P   Shen Huali H  

Analytical chemistry 20191219 1


Protein N-glycosylation is ubiquitous in the brain and is closely related to cognition and memory. Alzheimer's disease (AD) is a multifactorial disorder that lacks a clear pathogenesis and treatment. Aberrant N-glycosylation has been suggested to be involved in AD pathology. However, the systematic variations in protein N-glycosylation and their roles in AD have not been thoroughly investigated due to technical challenges. Here, we applied multilayered N-glycoproteomics to quantify the global pr  ...[more]

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