Neurodegeneration‐related amyloids interact with the prion protein

Abstract

Tau protein is the major component of intracellular aggregates that characterize a number of neurodegenerative disorders collectively called tauopathies. Tau amyloids propagate from cell to cell through different routes, such as dynamin‐dependent endocytosis, actin‐dependent macropinocytosis, tunneling nanotubes. Here, we evaluate the role of the prion protein PrPC in promoting the internalization of synthetic tau aggregates in cultured cells. As previously found by our group, the prion protein facilitates the uptake of synuclein fibrils in neuroblastoma cell lines, in primary neurons and in mice. Using confocal microscopy, we show that also tau fibrils take advantage of the presence of the prion protein on the plasma membrane to gain entrance to the cell, and that antibodies directed against the binding site of the fibrils on PrPC can decrease the internalization of the aggregates. Moreover, tau fibrils interact with both the cellular form PrPC and the pathological conformer PrPSc, inducing clearance of the latter through a combination of lysosomal activation and inhibition of prion conversion. Our results indicate that the prion protein can act as a receptor for aggregated proteins (synuclein, tau), and that targeting PrPC could be a therapeutic strategy to slow down the spreading of tau pathology.Support or Funding InformationThis work was supported by the Program FIRB (Prot. RBAP11FRE9_001).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.