Effects of neuron-derived a-synuclein in oligodendrocytes [RNA-Seq]
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ABSTRACT: Synucleinopathies, including multiple system atrophy (MSA) and Parkinson's disease (PD), are characterized by intracellular accumulation of α-synuclein (αSyn) aggregates. Despite oligodendrocytes' low expression of αSyn, αSyn aggregates in MSA cause glial cytoplasmic inclusions (GCIs). Here, we show that GCI development is facilitated by αSyn propagation from neurons to oligodendrocytes via Toll-like receptor 2 (TLR2). Demyelination-related characteristics in MSA oligodendrocytes and experimental models were identified by transcriptome studies. NM-101 treatment reversed the demyelination phenotype in the transgenic mouse model. These results point to anti-TLR2 immunotherapy as a possible MSA disease-modifying strategy.
ORGANISM(S): Mus musculus
PROVIDER: GSE312641 | GEO | 2025/12/10
REPOSITORIES: GEO
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