Fig 2: Cortical GML proteome profiling. (A) Volcano plot displaying the distribution of all proteins (n = 1182) with relative protein abundance (Log2 fold change) plotted against significance level (-Log10 P-Value). Significantly upregulated (red circle) as well as downregulated (blue circle) proteins in GMLs are also indicated. (B) Cellular identity of the significantly dysregulated GML proteins (upregulated and downregulated). (C) Venn diagram comparison of DEPs (p < 0.05) between WMLs and GMLs. (D) IPA canonical pathways, activated (red) and inhibited (blue), associated with significantly dysregulated proteins in GMLs. (E) LFQ-based heat map of mitochondria-specific downregulated proteins in GMLs. Proteins that are common and have opposite expressions in WML proteomic data are highlighted in red. (F) PPI network analysis of downregulated proteins showing enrichment of mitochondria-related pathways. (G) MCODE analysis revealed a highly interconnected sub-network associated with oxidative phosphorylation. (H–L) PLP- stained image of (H) sub-pial lesion. IHC images showing reduced expression of NDUFA5 (I,J) and ATP5L (K,L) in demyelinated regions (red box) compared to NAGM (blue box). Scale bar- 500µm (H) and 100µm (I–L).