In vitro recapitulation of aberrant protein inclusions in neurodegenerative diseases

Abstract

Aberrant protein aggregates in affected brain cells of patients with neurodegenerative diseases are a well-known hallmark, but although the formation of these inclusions is an important pathogenic event, the mechanism involved remains unclear. We have recently established a simple method to introduce protein fibrils into cultured cells as seeds for protein aggregation, and we showed that intracellular soluble α-synuclein or tau can aggregate in cultured cells dependently upon seeds introduced in this way. Seeded aggregation of α-synuclein induced necrotic cell death, which was suppressed by the addition of various polyphenols. Our cellular models are expected to be valuable tools not only for elucidating the molecular mechanisms of onset of neurodegenerative diseases, but also for drug discovery. 

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