While it still isn’t conclusively known how prions kill brain cells, one of the most widely accepted hypotheses is that prion proteins (PrPC) normally sit on the surface of the cell, but if a PrPC is misfolded (idiopathically, acquired, or genetically) before it reaches the cell’s surface, the cell’s quality control mechanism sends it to the cytosol to be destructed. However, it takes only a very small amount of the misfolded PrPC (PrPRes/PrPSc) in the cytosol to overwhelm the cell’s quality control mechanism in order to cause the death of the neuron.
