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Báo cáo Y học: Toxicity of novel C-terminal prion protein fragments and peptides harbouring disease-related C-terminal mutations

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Mice expressing a C-terminal fragment of the prion protein instead of wild-type prion protein die from massive neuronal degeneration within weeks of birth. The C-terminal region of PrPc (PrP121–231) expressed in these mice has an intrinsic neurotoxicity to cultured neurones. Unlike PrPSc, which is not neurotoxic to neurones lacking PrPc expression, PrP121–231 was more neurotoxic to PrPc-deficient cells. Human mutations E200K and F198S were found to enhance toxicity of PrP121–231 to PrP-knockout neurones and E200K enhanced toxicity to wild-type neurones. The normal metabolic cleavage point of PrPc is approximately aminoacid residue 113. A fragment of PrPc corresponding to the whole.

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