Electroacupuncture alleviates Parkinson’s disease via promoting METTL9-catalyzed histidine methylation of NF-κB

Abstract

This study aimed to investigate the effects of electroacupuncture (EA) treatment on PD. MPTP administration was used establish PD mice model. The number of neurons was determined using TH staining. mRNA expression was detected using RT-qPCR. Protein expression was detected using western blot. Gene expression was determined using immunofluorescence and immunohistochemistry. The functions of neurons were determined using TUNEL and flow cytometry assay. The binding sites on NF-κB RELA in the promoter of NLRP3 was predicted by JASPAR and verified by luciferase and ChIP assays. EA treatment improved motor dysfunction in patients with PD. In vivo assays showed that MPTP administration induced the loss of neurons in mice, which was restored by EA treatment. Moreover, EA treatment attenuates motor deficits in MPTP-induced PD mice. EA treatment also inhibited the enrichment of pro-inflammatory cytokines and LDH, and suppressed neuronal pyroptosis. EA treatment increased the expression of METTL9. However, METTL9 deficiency dampened the effects of EA treatment and induced neuronal pyroptosis. Additionally, METTL9 promoted histidine methylation of NF-κB RELA, resulting the inhibition of epigenetic transcription of NLRP3. EA treatment restored neuronal function and improved motor dysfunction via promoting METTL9 histidine methylation of NF-κB/NLRP3 signaling.