Proteomics

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Characterization and chemoproteomic profiling of protein O-GlcNAcylation in SOD1-G93A mouse model


ABSTRACT: ALS is a devastating motor neuron disease. Protein O-linked β-N-acetylglucosamine (O-GlcNAc) modification has been found to affect the processing of several important proteins implicated in ALS. However, the O-GlcNAcylated proteome remains unexplored during ALS progression. Herein, we probed the dynamic changes of O-GlcNAcylation in SOD-G93A mice, the most widely used animal model for studying ALS pathogenesis. We discovered that the overall O-GlcNAc level is significantly decreased at the disease end stage. Correlatively, a great increase of OGA was observed. By using isoPTOP, a recently reported chemoproteomics strategy, we furthermore reported the identification of 568 high-confidence O-GlcNAc sites from end-stage SOD1-G93A and NTG mice. Of the 568 sites, 226—many of which occurred on neuronal function and structure-related proteins—were found to be dynamically regulated. These results provide a valuable resource for dissecting the functional role of O-GlcNAcylation in ALS and shed light on promising therapeutic avenues for ALS.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Spinal Cord

SUBMITTER: Yi Hao  

LAB HEAD: Yansu Guo

PROVIDER: PXD059664 | Pride | 2025-05-07

REPOSITORIES: Pride

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Characterization and chemoproteomic profiling of protein O-GlcNAcylation in SOD1-G93A mouse model.

Hao Yi Y   Li Zhongzhong Z   Du Xinyan X   Xie Qingsong Q   Li Dongxiao D   Lei Shaoyuan S   Guo Yansu Y  

Molecular medicine (Cambridge, Mass.) 20250228 1


<h4>Background</h4>Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron disease. Protein O-linked β-N-acetylglucosamine (O-GlcNAc) modification has been found to affect the processing of several important proteins implicated in ALS. However, the overall level and cellular localization of O-GlcNAc during ALS progression are incompletely understood, and large-scale profiling of O-GlcNAcylation sites in this context remains unexplored.<h4>Methods</h4>By using immunostaining analysis an  ...[more]

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