Investigating the conformational stability of prion strains through a kinetic replication model.

Prion proteins are known to misfold into a range of different aggregated forms, showing different phenotypic and pathological states. Understanding strain specificities is an important problem in the field of prion disease. Little is known about which PrP(Sc) structural properties and molecular mech...

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Autores principales:	Mattia Zampieri, Giuseppe Legname, Claudio Altafini
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/02b61d6446504e58aa83389939e67aa5
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spelling	oai:doaj.org-article:02b61d6446504e58aa83389939e67aa52021-11-25T05:42:19ZInvestigating the conformational stability of prion strains through a kinetic replication model.1553-734X1553-735810.1371/journal.pcbi.1000420https://doaj.org/article/02b61d6446504e58aa83389939e67aa52009-07-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19578427/pdf/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Prion proteins are known to misfold into a range of different aggregated forms, showing different phenotypic and pathological states. Understanding strain specificities is an important problem in the field of prion disease. Little is known about which PrP(Sc) structural properties and molecular mechanisms determine prion replication, disease progression and strain phenotype. The aim of this work is to investigate, through a mathematical model, how the structural stability of different aggregated forms can influence the kinetics of prion replication. The model-based results suggest that prion strains with different conformational stability undergoing in vivo replication are characterizable in primis by means of different rates of breakage. A further role seems to be played by the aggregation rate (i.e. the rate at which a prion fibril grows). The kinetic variability introduced in the model by these two parameters allows us to reproduce the different characteristic features of the various strains (e.g., fibrils' mean length) and is coherent with all experimental observations concerning strain-specific behavior.Mattia ZampieriGiuseppe LegnameClaudio AltafiniPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 5, Iss 7, p e1000420 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Mattia Zampieri Giuseppe Legname Claudio Altafini Investigating the conformational stability of prion strains through a kinetic replication model.
description	Prion proteins are known to misfold into a range of different aggregated forms, showing different phenotypic and pathological states. Understanding strain specificities is an important problem in the field of prion disease. Little is known about which PrP(Sc) structural properties and molecular mechanisms determine prion replication, disease progression and strain phenotype. The aim of this work is to investigate, through a mathematical model, how the structural stability of different aggregated forms can influence the kinetics of prion replication. The model-based results suggest that prion strains with different conformational stability undergoing in vivo replication are characterizable in primis by means of different rates of breakage. A further role seems to be played by the aggregation rate (i.e. the rate at which a prion fibril grows). The kinetic variability introduced in the model by these two parameters allows us to reproduce the different characteristic features of the various strains (e.g., fibrils' mean length) and is coherent with all experimental observations concerning strain-specific behavior.
format	article
author	Mattia Zampieri Giuseppe Legname Claudio Altafini
author_facet	Mattia Zampieri Giuseppe Legname Claudio Altafini
author_sort	Mattia Zampieri
title	Investigating the conformational stability of prion strains through a kinetic replication model.
title_short	Investigating the conformational stability of prion strains through a kinetic replication model.
title_full	Investigating the conformational stability of prion strains through a kinetic replication model.
title_fullStr	Investigating the conformational stability of prion strains through a kinetic replication model.
title_full_unstemmed	Investigating the conformational stability of prion strains through a kinetic replication model.
title_sort	investigating the conformational stability of prion strains through a kinetic replication model.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/02b61d6446504e58aa83389939e67aa5
work_keys_str_mv	AT mattiazampieri investigatingtheconformationalstabilityofprionstrainsthroughakineticreplicationmodel AT giuseppelegname investigatingtheconformationalstabilityofprionstrainsthroughakineticreplicationmodel AT claudioaltafini investigatingtheconformationalstabilityofprionstrainsthroughakineticreplicationmodel
_version_	1718414498627321856

Investigating the conformational stability of prion strains through a kinetic replication model.

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