NR ABHT
AU Bessen,R.A.; Raymond,G.J.; Caughey,B.W.
TI In situ formation of protease-resistant prion protein in transmissible spongiform encephalopathy-infected brain slices
QU The Journal of Biological Chemistry 1997 Jun 13; 272(24): 15227-31
IA http://www.jbc.org/cgi/content/full/272/24/15227
PT journal article
AB The transmissible spongiform encephalopathies (TSEs) comprise a group of fatal neurodegenerative diseases that are characterized by the conversion of the normal host cellular prion protein (PrPc), to the abnormal protease-resistant prion protein isoform (PrPres). It has been proposed, though not proven, that the infectious TSE agent consists solely of PrPres and that PrPres-induced conformational conversion of PrPc to additional PrPres represents agent replication. In this study we demonstrate in situ conversion of protease-sensitive PrPc to PrPres in TSE-infected brain slices. One step in this process is the binding of soluble PrPc to endogenous PrPres deposits. The newly formed PrPres associated with the slices in a pattern that correlated with the pre-existing brain distribution of PrPres. Punctate in situ PrP conversion was observed in brain regions containing PrPres amyloid plaques, and a more dispersed conversion product was detected in areas containing diffuse PrPres deposits. These studies provide direct evidence that PrPres formation involves the incorporation of soluble PrPc into both nonfibrillar and fibrillar PrPres deposits in TSE-infected brain. Our findings suggest that the in situ PrP conversion reaction leads to additional polymerization of endogenous PrPres aggregates and is analogous to the process of PrPres fibril and subfibril growth in vivo.
MH Animals; Brain/*metabolism; Cricetinae; Endopeptidases/*metabolism; Immunohistochemistry; Mesocricetus; Prion Diseases/*metabolism; Prions/*metabolism; Research Support, U.S. Gov't, P.H.S.
AD Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, NIAID, National Institutes of Health, Hamilton, Montana 59840, USA
SP englisch
PO USA