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Lookup NU author(s): Professor Tiago OuteiroORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
© 2023 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry. The discovery of prions has challenged dogmas and has revolutionized our understanding of protein-misfolding diseases. The concept of self-propagation via protein conformational changes, originally discovered for the prion protein (PrP), also applies to other proteins that exhibit similar behavior, such as alpha-synuclein (aSyn), a central player in Parkinson's disease and in other synucleinopathies. aSyn pathology appears to spread from one cell to another during disease progression, and involves the misfolding and aggregation of aSyn. How the transfer of aSyn between cells occurs is still being studied, but one important hypothesis involves receptor-mediated transport. Interestingly, recent studies indicate that the cellular prion protein (PrPC) may play a crucial role in this process. PrPC has been shown to act as a receptor/sensor for protein aggregates in different neurodegenerative disorders, including Alzheimer's disease and amyotrophic lateral sclerosis. Here, we provide a comprehensive overview of the current state of knowledge regarding the interaction between aSyn and PrPC and discuss its role in synucleinopathies. We examine the properties of PrP and aSyn, including their structure, function, and aggregation. Additionally, we discuss the current understanding of PrPC's role as a receptor/sensor for aSyn aggregates and identify remaining unanswered questions in this area of research. Ultimately, we posit that exploring the interaction between aSyn and PrPC may offer potential treatment options for synucleinopathies. (Figure presented.)
Author(s): Vieira TCRG, Barros CA, Domingues R, Outeiro TF
Publication type: Review
Publication status: Published
Journal: Journal of Neurochemistry
Year: 2024
Volume: 168
Issue: 8
Pages: 1625-1639
Print publication date: 01/08/2024
Online publication date: 19/10/2023
Acceptance date: 01/10/2023
ISSN (print): 0022-3042
ISSN (electronic): 1471-4159
Publisher: John Wiley and Sons Inc
URL: https://doi.org/10.1111/jnc.15992
DOI: 10.1111/jnc.15992
Data Access Statement: Not applicable.
