Alternative Pathway for Methyl Supply through the Coupling of SHMT1 and PEMT to Maintain Astrocytic Homeostasis in Parkinson's Disease.

ABSTRACT: Serine Hydroxymethyltransferase 1 (SHMT1) plays a pivotal role in one-carbon metabolism, facilitating the production of SAM. In this study, dysregulation of one-carbon metabolism is reported in both Parkinson's disease (PD) patients and animal models, characterized by significantly downregulated expression of SHMT1. Astrocyte-specific conditional knockout of Shmt1 decreased SAM level, exacerbated motor dysfunction, and dopaminergic neuronal loss in a PD mouse model. While SAM is conventionally generated through the one-carbon cycle, the data indicate that, despite significant alterations in SHMT1, SAM remains unaffected while labeled ¹³C-Serine. Intriguingly, isotopic labeling experiments revealed a significant association between SHMT1 and the production of PDME, an intermediat

SUBMITTER: Chen YH 

PROVIDER: S-EPMC12866788 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature