Altered toxicity of the prion protein peptide PrP106-126 carrying the Ala(117)-->Val mutation.

Content Provider	Semantic Scholar
Author	Brown, David R.
Copyright Year	2000
Abstract	The inherited prion diseases such as Gerstmann-Sträussler-Scheinker syndrome (GSS) are linked to point mutations in the gene coding for the cellular isoform of the prion protein (PrP(C)). One particular point mutation A117V (Ala(117)-->Val) is linked to a variable pathology that usually includes deposition of neurofibrillary tangles. A prion protein peptide carrying this point mutation [PrP106-126(117V)] was generated and compared with a peptide based on the normal human sequence [PrP106-126(117A)]. The inclusion of this point mutation increased the toxicity of PrP106-126 which could be linked to an increased beta-sheet content. An assay of microtubule formation in the presence of tau indicated that PrP106-126 decreased the rate of microtubule formation that could be related to the displacement of tau. PrP106-126 carrying the 117 mutation was more efficient at inhibiting microtubule formation. These results suggest a possible mechanism of toxicity for protein carrying this mutation via destabilization of the cytoskeleton and deposition of tau in filaments, as observed in GSS.
File Format	PDF HTM / HTML
DOI	10.1042/0264-6021:3460785
PubMed reference number	10698707
Journal	Medline
Volume Number	346
Part	3
Alternate Webpage(s)	http://www.biochemj.org/content/ppbiochemj/346/3/785.full.pdf
Alternate Webpage(s)	https://doi.org/10.1042/0264-6021%3A3460785
Journal	The Biochemical journal
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article