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Synthetic Prion Selection and Adaptation.

Edoardo Bistaffa^1,2, Fabio Moda², Tommaso Virgilio^2,3

¹Laboratory of Prion Biology, Department of Neuroscience, Scuola Internazionale Superiore di Studi Avanzati (SISSA), Trieste, Italy.

Molecular Neurobiology

|August 4, 2018

Summary

This summary is machine-generated.

Prions adapt their conformation based on the replication environment, a process called prion selection or adaptation. This study demonstrates how synthetic prions change properties in vivo and in vitro, highlighting the role of replication context.

Keywords:

Adaptation PMCA Prion RT-QuIC Selection Synthetic prion

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Area of Science:

Neuroscience
Biochemistry
Molecular Biology

Background:

Prion diseases involve the misfolding of cellular prion protein (PrP^C) into infectious PrP^Sc.
PrP^Sc can adopt various conformations linked to distinct disease phenotypes.
Evidence suggests prions adapt their conformation to replication environments, known as prion selection or adaptation.

Purpose of the Study:

To investigate how a synthetically generated prion isolate changes its properties based on the replication context.
To analyze the phenomenon of prion selection and adaptation in vivo and in vitro.

Main Methods:

Protein Misfolding Cyclic Amplification (PMCA) was used to generate and propagate prions.
In vivo prion transmission studies were conducted in animals.
Biochemical, biophysical, and neuropathological assays were employed to characterize prion isolates.

Main Results:

A synthetic prion isolate adapted its biochemical and biophysical properties in the second passage in vivo.
Two distinct prion isolates (PrP^Sc-M and PrP^Sc-D) emerged with different glycosylation patterns.
PMCA analysis of these isolates generated a new prion (PrP^Sc-PMCA) with distinct properties, suggesting selective amplification.

Conclusions:

The replication environment critically influences prion selection and adaptation.
PMCA can mimic in vitro prion replication, offering a tool to study environmental influences on prion adaptation.