Bibliographic Details
| Title: |
Characterization and chemoproteomic profiling of protein O-GlcNAcylation in SOD1-G93A mouse model |
| Authors: |
Yi Hao, Zhongzhong Li, Xinyan Du, Qingsong Xie, Dongxiao Li, Shaoyuan Lei, Yansu Guo |
| Source: |
Molecular Medicine, Vol 31, Iss 1, Pp 1-14 (2025) |
| Publisher Information: |
BMC, 2025. |
| Publication Year: |
2025 |
| Collection: |
LCC:Therapeutics. Pharmacology
LCC:Biochemistry |
| Subject Terms: |
O-linked β-N-acetylglucosamine (O-GlcNAc), Chemoproteomics, Amyotrophic lateral sclerosis (ALS), SOD1-G93A mice, Chemoenzymatic labeling, Click chemistry, Therapeutics. Pharmacology, RM1-950, Biochemistry, QD415-436 |
| More Details: |
Abstract Background 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. Methods By using immunostaining analysis and chemoenzymatic labeling-based quantitative chemoproteomics, we assayed O-GlcNAcylation dynamics of lumbar spinal cords from SOD-G93A mice and their non-transgenic (NTG) littermates, the most widely used animal model for studying ALS pathogenesis. Results We discovered that the global O-GlcNAcylation was significantly reduced at the disease end stage. Correlatively, a great increase of OGA was observed. Immunohistochemistry and immunofluorescence analysis showed a higher proportion of O-GlcNAc-positive neurons in the NTG group, while O-GlcNAc colocalization with astrocytes/microglia was elevated in SOD1-G93A mice. Moreover, we 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. Conclusion These data provide a valuable resource for dissecting the functional role of O-GlcNAcylation in ALS and shed light on promising therapeutic avenues for ALS. The chemoenzymatic labeling-based chemoproteomic approach is applicable for probing O-GlcNAc dynamics in various pathological processes. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1528-3658 |
| Relation: |
https://doaj.org/toc/1528-3658 |
| DOI: |
10.1186/s10020-025-01134-4 |
| Access URL: |
https://doaj.org/article/a5f3a1a186574b6ab5daa003247e52f6 |
| Accession Number: |
edsdoj.5f3a1a186574b6ab5daa003247e52f6 |
| Database: |
Directory of Open Access Journals |
