PrP meets alpha-synuclein: Molecular mechanisms and implications for disease.

Autor: Vieira TCRG; Institute of Medical Biochemistry Leopoldo de Meis and National Institute of Science and Technology for Structural Biology and Bioimaging, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Barros CA; Institute of Medical Biochemistry Leopoldo de Meis and National Institute of Science and Technology for Structural Biology and Bioimaging, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Domingues R; Department of Experimental Neurodegeneration, Center for Biostructural Imaging of Neurodegeneration, University Medical Center Göttingen, Göttingen, Germany., Outeiro TF; Department of Experimental Neurodegeneration, Center for Biostructural Imaging of Neurodegeneration, University Medical Center Göttingen, Göttingen, Germany.; Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.; Faculty of Medical Sciences, Translational and Clinical Research Institute, Newcastle University, Newcastle Upon Tyne, UK.; Scientific Employee with an Honorary Contract at Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Göttingen, Germany.
Jazyk: angličtina
Zdroj: Journal of neurochemistry [J Neurochem] 2024 Aug; Vol. 168 (8), pp. 1625-1639. Date of Electronic Publication: 2023 Oct 19.
DOI: 10.1111/jnc.15992
Abstrakt: 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 (PrP C ) may play a crucial role in this process. PrP C 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 PrP C 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 PrP C '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 PrP C may offer potential treatment options for synucleinopathies.
(© 2023 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.)
Databáze: MEDLINE
Externí odkaz: