Antibodies directed against a specific sequence of amino acids in the prion protein can selectively recognize the disease-associated variant, but not the normal cellular prion protein, Neil Cashman and colleagues report in the July issue of Nature Medicine. The finding may lead to new diagnostics and therapy for prion diseases.
Prion diseases are a group of neurodegenerative disorders characterized by loss of brain cells, spongy degeneration of the brain, and accumulation of glial cells and abnormal amyloid protein. They include scrapie in sheep, bovine spongiform encephalopathy or ‘mad cow’ disease in cattle, chronic wasting disease in deer and elk, and kuru and Creutzfeldt-Jakob disease in humans.
Current dogma holds that the diseases are caused by pathological misfolding of a cellular prion protein (PrPC) into the disease-associated isoform (PrPSc). Assuming that the misfolded structure might expose a normally hidden side of the prion protein to the environment, the researchers tried to develop antibodies specific to the disease variant.
The amino acid sequence Tyr-Tyr-Arg is exposed in the misfolded prion, but not in the cellular prion protein, the researchers found. The finding allows researchers to probe the distribution and structure of misfolded prion proteins and may lead to new clinical applications.
Neil R. Cashman (University of Toronto, Ontario, Canada)
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(C) Nature Medicine press release.
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