Integrative analysis of metabolomics and proteomics unravels purine metabolism dysregulation in the SOD1G93A mouse model of amyotrophic lateral sclerosis

• DOI: 10.1016/j.nbd.2023.106110
• Publication Date: 2023-03-29T16:02:15Z
• Authors: Xiaojiao Xu; Qiu Yang; Zheyi Liu; Rong Zhang; Hang Yu; Manli Wang; Sheng Chen; Guowang Xu; Yaping Shao; Weidong Le
• Keywords: Metabolic pathway

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with progressive paralysis of limbs and bulb in patients, the cause which remains unclear. Accumulating studies suggest that motor neuron degeneration associated systemic metabolic impairment ALS. However, reprogramming underlying mechanism longitudinal progression remain poorly understood. In this study, we aimed to investigate molecular changes at both proteomic levels during identify most critical pathways mechanisms involved ALS pathophysiological changes. Utilizing liquid chromatography-mass spectrometry-based metabolomics, analyzed metabolites' plasma, lumbar spinal cord, cortex from SOD1G93A mice wildtype (WT) littermates different stages. To elucidate regulatory network changes, further proteomics profile cords WT mice. A group metabolites implicated purine metabolism, methionine cycle, glycolysis were found differentially expressed mice, abnormal expressions enzymes these also confirmed. Notably, first demonstrated dysregulation metabolism might contribute pathogenesis Furthermore, discovered fatty acid TCA arginine proline folate-mediated one‑carbon significantly altered disease. The identified differential proteins our study could complement existing data on ALS, provide new insight into pathological novel therapeutic targets