Fig 2: Protein–protein interactions of alpha-synuclein and MOBP or HIP1 in cerebellar white matter of patients with MSA (N = 2). Proximity ligation assay was performed to investigate protein–protein interactions of a-synuclein and MOBP or HIP1. In the absence of primary antibodies, no signals were detected in the cytoplasm of oligodendroglia (A, C). In patients with MSA, discrete signals in GCIs were observed (B, D), indicating the protein–protein interactions of a-synuclein and MOBP (B; black arrowheads) and HIP1 (D; black arrows).

Fig 3: Scatterplots illustrating CpGs with significant DNA methylation‐expression correlations. (A) Six CpGs in MOBP with significant DNA methylation‐expression correlations (MSA + CTRL, r ≤ −0.411, p < 0.05). (B) Six CpGs in HIP1 with significant DNA methylation‐expression correlations overall or in either MSA or healthy controls individually, most of which highlighting opposite correlation signals between MSA and healthy controls. CTRL, healthy controls; MSA, multiple system atrophy

Fig 4: Boxplots showing gene expression levels for MOBP and HIP1 across major brain cell types in healthy control brains. A, astrocytes; E, endothelial cells; FA, foetal astrocytes; M, microglia; N, neurons; O, oligodendrocytes

Fig 5: Shared protein interactors for a-synuclein (SNCA), HIP1 and MOBP identified through the construction of a protein–protein interaction network using IPA. APP, amyloid precursor protein; AP1B1, adaptor-related protein complex 1 subunit beta 1; AP2A1, adaptor-related protein complex 2 subunit alpha 1; CLTC, clathrin heavy chain; CP, canonical pathways; DYRK1A, dual specificity tyrosine phosphorylation-regulated kinase 1A; EGFR, epidermal growth factor receptor; HTT, huntingtin; RPS10, ribosomal protein S10; TRAF6, TNF receptor-associated factor 6; UBC, ubiquitin C; VIRMA, vir like m6A methyltransferase associated