The role of exosomes in prion diseases
Francesca PROPERZI
(Istituto Superiore di Sanità)
Transmissible spongiform encephalopathy (TSE) or prion diseases are fatal rare neurodegenerative disorders affecting man and animals and caused by a transmissible infectious agent. A number of in vitro studies have suggested that the spread of prion infectivity in between cells and across different tissues and body fluids could occur via the exosomal pathway. Prions are indeed released from infected murine N2a and RK13 cells in association with exosomes. Interestingly, moloney murine leukemia virus infection strongly enhances the release of prion infectivity in the supernatant of co-infected cells via exosomal recruitment. Hematopoietic cells secrete exosome-associated prions with possible crucial implications in the spreading across the body.
Interestingly, in most forms of prion diseases, blood is infectious, but detection by immunochemistry techniques of the only available marker of infection (the misfolded prion protein, PrPTSE) in blood has been elusive for many years. We recently found that PrPTSE is associated with plasma exosomes. However, further purification of the exosomes on a sucrose gradient was necessary to remove plasma immunoglobulins, which interfere with PrPTSE, masking its detection by immunochemistry.
