Fig. 2From: Animal modeling an oligodendrogliopathy – multiple system atrophyInsights into MSA pathophysiology. The sequence of pathological events of MSA is now recognized as abnormal protein aggregations (GCIs) in oligodendrocytes first, followed by demyelination and then neurodegeneration and loss of neurons. GCIs are predominantly composed of α-synuclein. Early features of MSA pathogenesis include decline in glial neurotrophic factors, mictrotubule disruption, and activation of caspase 3 and microglial toll-like receptor 4 (TLR4). Late features of MSA pathogenesis include accumulation of lysosomes and cytoplasmic myelin fragments in oligodendrocytes, increased production of cytokines from activated microglia, and astrogliosisBack to article page