Murine scrapie-infected neurons in vivo release excess prion protein into the extracellular space.
An originally heretical proposition that the transmissible spongiform encephalopathies are caused by a host-coded protein (the prion hypothesis) is now current dogma. Indeed these disorders are commonly called prion diseases but the prion hypothesis provides no readily acceptable explanation for the source of the informational component of the agent necessary to code for the diversity of strains of scrapie. Ultrastructural immunolocalisation of prion protein (PrP) in murine scrapie shows that PrP accumulates in association with the plasmalemma of neurones, diffusing from the neuronal cell surface into the extracellular space around small neurites prior to aggregation and fibril assembly. These events occur without the involvement of other cell types. The area of neuropil infiltrated with extracellular PrP around infected neurons and neurites indicates that the form of PrP initially produced is not immediately amyloidogenic.
Lasswade Veterinary Laboratory, Midlothian, Scotland, UK.
M
M
Jeffrey
C M
CM
Goodsir
M E
ME
Bruce
P A
PA
McBride
N
N
Fowler
J R
JR
Scott
D000818:Animals; D001921:Brain / Q000382:microbiology / Q000473:pathology; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D009474:Neurons / Q000378:metabolism* / Q000382:microbiology / Q000648:ultrastructure; D018621:PrPC Proteins / Q000378:metabolism*; D011328:Prions / Q000378:metabolism*; D012608:Scrapie / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology
D018621:PrPC Proteins; D011328:Prions