The Dynamics of Prion Spreading is Governed by the Interplay Between the Non-linearities of Tissue Response and Replication Kinetics

Overview

Journal iScience

Publisher Cell Press

Date 2024 Dec 24

PMID 39717079

Authors

Basile Fornara

Angelique Igel

Vincent Beringue

Davy Martin

Pierre Sibille

Laurent Pujo-Menjouet

Human Rezaei

Affiliations

Soon will be listed here.

Abstract

Prion diseases, or transmissible spongiform encephalopathies (TSEs), are neurodegenerative disorders caused by the accumulation of misfolded conformers (PrP) of the cellular prion protein (PrP). During the pathogenesis, the PrP seeds disseminate in the central nervous system and convert PrP leading to the formation of insoluble assemblies. As for conventional infectious diseases, variations in the clinical manifestation define a specific prion strain which correspond to different PrP structures. In this work, we implemented the recent developments on PrP structural diversity and tissue response to prion replication into a stochastic reaction-diffusion model using an application of the Gillespie algorithm. We showed that this combination of non-linearities can lead prion propagation to behave as a complex system, providing an alternative to the current paradigm to explain strain-specific phenotypes, tissue tropisms, and strain co-propagation while also clarifying the role of the connectome in the neuro-invasion process.

References

Tanaka M, Yamasaki T, Hasebe R, Suzuki A, Horiuchi M . Enhanced phosphorylation of PERK in primary cultured neurons as an autonomous neuronal response to prion infection. PLoS One. 2020; 15(6):e0234147. PMC: 7263615. DOI: 10.1371/journal.pone.0234147. View

Walker L, Schelle J, Jucker M . The Prion-Like Properties of Amyloid-β Assemblies: Implications for Alzheimer's Disease. Cold Spring Harb Perspect Med. 2016; 6(7). PMC: 4930920. DOI: 10.1101/cshperspect.a024398. View

Fornari S, Schafer A, Kuhl E, Goriely A . Spatially-extended nucleation-aggregation-fragmentation models for the dynamics of prion-like neurodegenerative protein-spreading in the brain and its connectome. J Theor Biol. 2019; 486:110102. DOI: 10.1016/j.jtbi.2019.110102. View

Bessen R, Marsh R . Distinct PrP properties suggest the molecular basis of strain variation in transmissible mink encephalopathy. J Virol. 1994; 68(12):7859-68. PMC: 237248. DOI: 10.1128/JVI.68.12.7859-7868.1994. View

Igel-Egalon A, Moudjou M, Martin D, Busley A, Knapple T, Herzog L . Reversible unfolding of infectious prion assemblies reveals the existence of an oligomeric elementary brick. PLoS Pathog. 2017; 13(9):e1006557. PMC: 5589264. DOI: 10.1371/journal.ppat.1006557. View

Baldwin M, Stahl N, Reinders L, Gibson B, Prusiner S, Burlingame A . Permethylation and tandem mass spectrometry of oligosaccharides having free hexosamine: analysis of the glycoinositol phospholipid anchor glycan from the scrapie prion protein. Anal Biochem. 1990; 191(1):174-82. DOI: 10.1016/0003-2697(90)90405-x. View

Prusiner S . Novel proteinaceous infectious particles cause scrapie. Science. 1982; 216(4542):136-44. DOI: 10.1126/science.6801762. View

Beringue V, Vilotte J, Laude H . Prion agent diversity and species barrier. Vet Res. 2008; 39(4):47. DOI: 10.1051/vetres:2008024. View

Braak H, Del Tredici K . Alzheimer's pathogenesis: is there neuron-to-neuron propagation?. Acta Neuropathol. 2011; 121(5):589-95. DOI: 10.1007/s00401-011-0825-z. View

10.

Erban R, Chapman S . Stochastic modelling of reaction-diffusion processes: algorithms for bimolecular reactions. Phys Biol. 2009; 6(4):046001. DOI: 10.1088/1478-3975/6/4/046001. View

11.

Igel-Egalon A, Laferriere F, Moudjou M, Bohl J, Mezache M, Knapple T . Early stage prion assembly involves two subpopulations with different quaternary structures and a secondary templating pathway. Commun Biol. 2019; 2:363. PMC: 6778151. DOI: 10.1038/s42003-019-0608-y. View

12.

Legname G, Nguyen H, Peretz D, Cohen F, DeArmond S, Prusiner S . Continuum of prion protein structures enciphers a multitude of prion isolate-specified phenotypes. Proc Natl Acad Sci U S A. 2006; 103(50):19105-10. PMC: 1748184. DOI: 10.1073/pnas.0608970103. View

13.

Trusina A, Papa F, Tang C . Rationalizing translation attenuation in the network architecture of the unfolded protein response. Proc Natl Acad Sci U S A. 2008; 105(51):20280-5. PMC: 2603256. DOI: 10.1073/pnas.0803476105. View

14.

Chatterjee A, Kaznessis Y, Hu W . Tweaking biological switches through a better understanding of bistability behavior. Curr Opin Biotechnol. 2008; 19(5):475-81. PMC: 2766094. DOI: 10.1016/j.copbio.2008.08.010. View

15.

Griffith J . Self-replication and scrapie. Nature. 1967; 215(5105):1043-4. DOI: 10.1038/2151043a0. View

16.

Cronier S, Laude H, Peyrin J . Prions can infect primary cultured neurons and astrocytes and promote neuronal cell death. Proc Natl Acad Sci U S A. 2004; 101(33):12271-6. PMC: 514468. DOI: 10.1073/pnas.0402725101. View

17.

DeArmond S . Differential targeting of neurons by prion strains. Methods Mol Med. 2011; 59:85-110. DOI: 10.1385/1-59259-134-5:85. View

18.

Turing A . The chemical basis of morphogenesis. 1953. Bull Math Biol. 1990; 52(1-2):153-97; discussion 119-52. DOI: 10.1007/BF02459572. View

19.

Sorce S, Nuvolone M, Russo G, Chincisan A, Heinzer D, Avar M . Genome-wide transcriptomics identifies an early preclinical signature of prion infection. PLoS Pathog. 2020; 16(6):e1008653. PMC: 7360066. DOI: 10.1371/journal.ppat.1008653. View

20.

Mortberg M, Zhao H, Reidenbach A, Gentile J, Kuhn E, OMoore J . Regional variability and genotypic and pharmacodynamic effects on PrP concentration in the CNS. JCI Insight. 2022; 7(6). PMC: 8986079. DOI: 10.1172/jci.insight.156532. View