Newly Created Prion Seen As Exciting Research Tool

The neuropathology, replication potency, and biophysical profiling suggested that a novel, particularly neurotoxic human prion strain had been created.

By comparing the structural organization of these synthetic human prions with that of parent sCJD MM1 prions and noninfectious human prion protein amyloid, the investigators identified domains in PrP that were important for the initiation of replication in vivo, i.e. their infectivity, and for targeting of different anatomical brain structures.

“This accomplishment represents a watershed,” said senior author Dr. Jiri G. Safar, professor of pathology and neurology at the Case Western Reserve School of Medicine. “Until now our understanding of prions in the brain has been limited. Being able to generate synthetic human prions in a test tube as we have done will enable us to achieve a much richer understanding of prion structure and replication. This is crucial for developing inhibitors of their replication and propagation throughout the brain, which is essential for halting prion-based brain disease.”

“Our findings explain at the structural level the emergence of new human prions and provide a basis for understanding how seemingly subtle differences in misfolded protein structure and modifications affect their transmissibility, cellular targeting, and thus manifestation in humans,” said Dr. Safar.

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Case Western Reserve University School of Medicine