Image_1_Galectin-9/Tim-3 pathway mediates dopaminergic neurodegeneration in MPTP-induced mouse model of Parkinson’s disease.TIF

Galectin-9 (Gal-9) is a crucial immunoregulatory mediator in the central nervous system. Microglial activation and neuroinflammation play a key role in the degeneration of dopaminergic neurons in the substantia nigra (SN) in Parkinson’s disease (PD). However, it remains unknown whether Gal-9 is involved in the pathogenesis of PD. We found that MPP+ treatment promoted the expression of Gal-9 and pro-inflammatory cytokines (IL-6, IL-1β, TNF-α, and MIP-1α) in a concentration-dependent manner in BV2 cells. Gal-9 enhanced neurodegeneration and oxidative stress induced by MPP+ in SH-SY5Y cells and primary neurons. Importantly, deletion of Gal-9 or blockade of Tim-3 ameliorated microglial activation, reduced dopaminergic neuronal loss, and improved motor performance in an MPTP-induced mouse model of PD. These observations demonstrate a pathogenic role of the Gal-9/Tim-3 pathway in exacerbating microglial activation, neuroinflammation, oxidative stress, and dopaminergic neurodegeneration in the pathogenesis of PD.</p

Additional file 3 of Partial erosion on under-methylated regions and chromatin reprogramming contribute to oncogene activation in IDH mutant gliomas

Additional file 3. Table S2: The genomic context of phUMRs and fhUMRs

Additional file 1 of Partial erosion on under-methylated regions and chromatin reprogramming contribute to oncogene activation in IDH mutant gliomas

Additional file 1. Fig. S1: The refUMRs provide a better definition of hypermethylated regions in IDH mutant gliomas. Fig. S2: Partial hyper possess distinct features compared with flanking UMRs. Fig. S3: Chromatin features of fhUMRs and phUMRs. Fig. S4: GO and KEGG functional annotation of phUMR and fhUMR related genes. Fig. S5: Transcriptional tendency of phUMR and fhUMR genes in DKFZ. Fig. S6: Cell type enrichment analysis of phUMRs related genes. Fig. S7: Heatmaps of methylation signals at up- and down-regulated phUMR/fhUMR genes. Fig. S8: Histone modification changes in differentially expressed genes within phUMR or fhUMR. Fig. S9: Local histone modification changes on partial Hyper and flanking UMR in phUMRs. Fig. S10: Partial methylation erosion on the promoter of glioma related genes. Fig. S11: Local changes of average histone modification signals at partial Hyper, flanking UMR and downstream regions of up-regulated oncogenes

Additional file 2 of Partial erosion on under-methylated regions and chromatin reprogramming contribute to oncogene activation in IDH mutant gliomas

Additional file 2. Table S1: Sample information of WGBS data