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bioRxiv · 10.1101/2020.01.19.911644

The uptake of tau amyloid fibrils is facilitated by the cellular prion protein and hampers prion propagation in cultured cells

De Cecco, E.·Celauro, L.·Vanni, S.·Grandolfo, M.·Aguzzi, A.·Legname, G.
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Abstract

Tauopathies are prevalent, invariably fatal brain diseases for which no cure is available. Tauopathies progressively affect the brain through cell-to-cell transfer of tau protein amyloids, yet the spreading mechanisms are unknown. Here we show that the cellular prion protein (PrPC) facilitates the uptake of tau aggregates by cultured cells, possibly by acting as an endocytic receptor. In mouse neuroblastoma cells, we found that tau amyloids bind to PrPC; internalization of tau fibrils was reduced in isogenic cells devoid of the gene encoding PrPC. Antibodies against N-proximal epitopes of PrPC impaired the binding of tau amyloids and decreased their uptake. Surprisingly, exposure of chronically prion-infected cells to tau amyloids reduced the accumulation of aggregated prion protein; this effect lasted for more than 72 hours after amyloid removal. These results point to bidirectional interactions between the two proteins: whilst PrPC mediates the entrance of tau fibrils in cells, PrPSc buildup is greatly reduced in their presence, possibly because of an impairment in the prion conversion process.

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De Cecco, E., Celauro, L., Vanni, S., Grandolfo, M., Aguzzi, A., Legname, G.. 2020-01-19. The uptake of tau amyloid fibrils is facilitated by the cellular prion protein and hampers prion propagation in cultured cells. https://doi.org/10.1101/2020.01.19.911644

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