Body-first Parkinson's disease and variant Creutzfeldt-Jakob disease - similar or different?

Abstract

In several neurodegenerative disorders, proteins that typically exhibit an α-helical structure misfold into an amyloid conformation rich in β-sheet content. Through a self-templating mechanism, these amyloids are able to induce additional protein misfolding, facilitating their propagation throughout the central nervous system. This disease mechanism was originally identified for the prion protein (PrP), which misfolds into PrPSc in a number of disorders, including variant Creutzfeldt-Jakob disease (vCJD) and bovine spongiform encephalopathy (BSE). More recently, the prion mechanism of disease was expanded to include other proteins that rely on this self-templating mechanism to cause progressive degeneration, including α-synuclein misfolding in Parkinson's disease (PD). Several studies now suggest that PD patients can be subcategorized based on where in the body misfolded α-synuclein originates, either the brain or the gut, similar to patients developing sporadic CJD or vCJD. In this review, we discuss the human and animal model data indicating that α-synuclein and PrPSc misfolding originates in the gut in body-first PD and vCJD, and summarize the data identifying the role of the autonomic nervous system in the gut-brain axis of both diseases.

• Authors: Amanda L Woerman, Gültekin Tamgüney
• Journal: Neurobiology of disease (Neurobiol Dis) Vol. 164 Pg. 105625 (03 2022) ISSN: 1095-953X [Electronic] United States
• PMID: 35026401 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Prion Proteins

Topics

• Animals
• Brain (metabolism, pathology)
• Creutzfeldt-Jakob Syndrome (metabolism, pathology)
• Disease Models, Animal
• Humans
• Neurons (metabolism, pathology)
• Parkinson Disease (metabolism, pathology)
• Prion Proteins (metabolism)