Oligodendrocytes may provide the extra density of α-synuclein filaments from multiple system atrophy

Oligodendrocyte-derived seeded α-synuclein filaments uniquely retain an extra non-proteinaceous density at the protofilament interface seen in multiple system atrophy seeds.

• Why it matters: The work addresses how MSA seeds template α-synuclein aggregation and what cellular factors contribute to the distinctive filament architecture that may enable brain spreading.
• What they did: MSA brain-derived α-synuclein filaments were used to seed aggregation in SH-SY5Y cells, human iNeurons, mixed murine cortical cultures, and oligodendrocyte-enriched murine primary cultures, all overexpressing human α-synuclein, followed by cryo-EM structure determination.
• The result: Seeds containing two protofilaments with an unidentified inter-protofilament density produced single-protofilament filaments in most models, while only oligodendrocyte-derived structures showed the extra density; striatal injection into oligodendrocyte-promoter transgenic mice yielded similar single-protofilament filaments with comparable extra density.

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