Molecular Cell: The first atomic-level imaging of deadly prions

The highest-resolution imaging of infectious prions ever provides the first atomic-level data on how these abnormal proteins assemble in humans and animals to cause deadly neurodegenerative diseases, and how they may become new treatments Goal

The research conducted by Case Western Reserve University and the National Institutes of Health (NIH) is available on molecular cells

"These detailed prion structures provide a new prerequisite for understanding and targeting these currently incurable diseases," said the lead and co-corresponding author of the study, Alison Alison, an assistant professor in the Department of Pathology at Case Western Reserve School of Medicine.

She said that seeing the basic components of these deadly proteins provides the basis for therapeutic strategies to prevent the spread, accumulation and toxicity of prions

Prion proteins in the brain tissue, spread their "misfolded irregularly shaped regular version of the same protein and the source of mammalian diseases, including human conditional Creutzfeldt-Jakob disease (CJD) and its variants, called vCJD disease, And Gerstmann-Straussler-Scheinker syndrome and so on

Similar prion-like mechanisms appear in other neurodegenerative diseases (including Parkinson's disease, amyotrophic lateral sclerosis or amyotrophic lateral sclerosis), chronic traumatic encephalopathy (CTE), and Alzheimer's Disease) in the characteristic protein in the development process

Although this is rare, prion diseases can spread from person to person; other diseases are easily spread between animals, such as chronic wasting disease

In this study, researchers extracted scrapie prions adapted to rodents from the brains of clinically diseased hamsters

High resolution

Use the cryo-electron microscope (cryo-EM) of the National Institutes of Health and the Cleveland Center for Structure and Membrane Biology, as well as the collaborative pipeline between Kraus (CWRU), Byron Caughey (NIH) and the Research Technology Division (NIH) to study A person can determine the basic components of these proteins, including the positions of their amino acids

By suspending prions in ice, cryogenic electronics allows researchers to take thousands of images of protein assembly and use proprietary software to build three-dimensional atomic resolution models

Kraus said this is the first successful imaging, reaching the atomic-level details of brain-derived prions, opening the door to similar "solving other prion structures

"It is thought that the structure of prions is very different because they are related to different diseases