Skip to main content
Fig. 4 | Molecular Neurodegeneration

Fig. 4

From: Multiple system atrophy: α-Synuclein strains at the neuron-oligodendrocyte crossroad

Fig. 4

Proposed pathogenesis of Multiple system atrophy. Following insults to neurons and oligodendrocytes, α-Synuclein expression in each cell type may be upregulated. Neuronal α-Synuclein secretion and oligodendrocyte α-Synuclein uptake increase due to alterations in membrane interactions and endocytosis pathways. In addition, TPPP/p25α localizes to the oligodendrocyte soma resulting in cellular swelling and reduced autophagy-lysosomal fusion. These conditions enable the formation of Multiple system atrophy (MSA) specific strains within oligodendrocyte cytosol, with the coalescence of strains leading to the formation of glial cytoplasmic inclusions. Altered Oligodendrocyte function is reflected by a reduction in neurotrophic support and the demyelination of neurons. The secretion of MSA α-Synuclein species results in the formation of neuronal cytoplasmic inclusions. Oligodendrocyte precursor cells may also take up α-Synuclein aggregates via altered endocytosis pathways, eventually giving rise to dysfunctional mature oligodendrocytes with a higher propensity to form glial cytoplasmic inclusions. Spreading strain pathology results in oligodendrocyte and neuron degeneration giving rise to oxidative stress, neuroinflammation and astrogliosis. These processes culminate into widespread glial cytoplasmic formation, neurodegeneration and MSA onset

Back to article page