Prion protein-overexpressing cells show altered response to a neurotoxic prion protein peptide

✍ Scribed by David R. Brown

• Book ID: 101245986
• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 154 KB
• Volume: 54
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/(sici)1097-4547(19981101)54:3<331::aid-jnr4>3.0.co;2-k

✦ Synopsis

A peptide fragment of the prion protein, PrP106-126 is toxic to neuronal cells in culture. This toxicity is dependent on neuronal expression of the prion protein (PrP c ) and also the presence of microglia. The role of expression of the PrP c in neurotoxicity of this peptide was investigated using mice that overexpress the prion protein. Cells derived from two different strains of PrP c -overexpressing mice were used (Tg20 and Tg35). PrP106-126 was more toxic to Tg35 cerebellar cells than wild-type or Tg20 cells. This increased toxicity required the presence of microglia. Analysis of microglia derived from wild-type and PrP c -overexpressing cells showed that Tg35 microglia were more easily activated than wild-type microglia, were more easily stimulated to proliferate by astrocytes, and had a higher level of PrP c expression. This may explain the increased PrP106-126 toxicity to Tg35 PrP c -overexpressing cerebellar cells. These results suggest that the toxicity of PrP106-126 may depend on the level of expression of PrP c by microglia as well as by neurones.