Proteinase-K-resistant prion protein isoforms in Gerstmann-Sträussler-Scheinker disease (Indiana kindred)

Journal of Neuropathology and Experimental Neurology
P PiccardoB Ghetti

Abstract

Gerstmann-Sträussler-Scheinker (GSS) disease is a cerebral prion protein (PrP) amyloidosis associated with mutations in the PrP gene (PRNP). A GSS disease variant with mutation at codon 198 (F198S) has been studied in a large Indiana kindred. Biochemical investigations showed that the amyloid protein consists of 11 and 7 kDa fragments of PrP. Immunohistochemical studies showed that in addition to amyloid, these patients accumulate PrP deposits which are neither fluorescent nor birefringent when stained with thioflavin S and Congo red. In the present paper, we analyzed proteinase-K (PK)-resistant PrP in 7 patients with GSS F198S disease. Immunoblots of PK-treated brain extracts show prominent bands of ca. 27-29, 18-19, and 8 kDa. Immunohistochemistry and thioflavin-S-fluorescence show that the amyloid deposits are conspicuous in the cerebellum but sparse in the caudate nucleus. However, immunoblot analysis reveals PK-resistant PrP bands of similar intensity in both regions. Treatment with PK and PNGase F generates a pattern similar to that of PK alone. Our findings suggest that brain extracts from GSS F198S disease contain 3 prominent nonglycosylated PK-resistant PrP fragments forming a pattern not previously described in other ...Continue Reading

Citations

Sep 13, 2003·The Journal of Biological Chemistry·Mario SalmonaFabrizio Tagliavini
May 4, 2017·Molecular Neurobiology·Andreu Matamoros-AnglesJosé Antonio Del Río
Jul 8, 1998·Proceedings of the National Academy of Sciences of the United States of America·P ParchiP Gambetti
Jan 24, 2014·International Journal of Cell Biology·Ilaria PoggioliniPiero Parchi
May 13, 2006·The Journal of General Virology·Mikael KlingebornTommy Linné

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