Dataset Information

Hingant2014 - Micellar On-Pathway Intermediate in Prion Amyloid Formation

ABSTRACT: Hingant2014 - Micellar On-Pathway Intermediate in Prion Amyloid Formation Hingant2014 - Micellar On-Pathway Intermediate in Prion Amyloid Formation Encoded non-curated model. Issues: - Missing kinetic parameters This model is described in the article: A micellar on-pathway intermediate step explains the kinetics of prion amyloid formation. Hingant E, Fontes P, Alvarez-Martinez MT, Arnaud JD, Liautard JP, Pujo-Menjouet L. PLoS Comput. Biol. 2014 Aug; 10(8): e1003735 Abstract: In a previous work by Alvarez-Martinez et al. (2011), the authors pointed out some fallacies in the mainstream interpretation of the prion amyloid formation. It appeared necessary to propose an original hypothesis able to reconcile the in vitro data with the predictions of a mathematical model describing the problem. Here, a model is developed accordingly with the hypothesis that an intermediate on-pathway leads to the conformation of the prion protein into an amyloid competent isoform thanks to a structure, called micelles, formed from hydrodynamic interaction. The authors also compare data to the prediction of their model and propose a new hypothesis for the formation of infectious prion amyloids. This model is hosted on BioModels Database and identified by: MODEL1409230001. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

DISEASE(S): Alzheimer's Disease

SUBMITTER: Audald Lloret i Villas

PROVIDER: MODEL1409230001 | BioModels | 2015-04-15

REPOSITORIES: BioModels

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Publications

A micellar on-pathway intermediate step explains the kinetics of prion amyloid formation.

Hingant Erwan E Fontes Pascaline P Alvarez-Martinez Maria Teresa MT Arnaud Jacques-Damien JD Liautard Jean-Pierre JP Pujo-Menjouet Laurent L

PLoS computational biology 20140807 8

In a previous work by Alvarez-Martinez et al. (2011), the authors pointed out some fallacies in the mainstream interpretation of the prion amyloid formation. It appeared necessary to propose an original hypothesis able to reconcile the in vitro data with the predictions of a mathematical model describing the problem. Here, a model is developed accordingly with the hypothesis that an intermediate on-pathway leads to the conformation of the prion protein into an amyloid competent isoform thanks to ...[more]

PMID: 25101755

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Project description:In human neurodegenerative diseases associated with the intracellular aggregation of Tau protein, the ordered cores of Tau filaments adopt distinct folds. Here, we analyze Tau filaments isolated from the brain of individuals affected by Prion-Protein cerebral amyloid angiopathy (PrP-CAA) and Gerstmann-Sträussler-Scheinker (GSS) disease, two genetically determined Prion protein (PrP) amyloidoses characterized by the deposition of PrP amyloid (APrP) in the vessel walls and in the cerebral parenchyma, respectively. A nonsense and a missense mutation in the PRNP gene lead to a premature termination of translation at codon position 160 (Q160Ter) of PrP in PrP-CAA, or to the substitution of an amino acid at residue 198 (F198S) of PrP in GSS. These two diseases have different clinical and pathologic phenotypes; however, in both diseases, neuropathologic analyses have consistently shown the presence of numerous neurofibrillary tangles (NFTs) made of filamentous Tau aggregates in neurons. We report that Tau filaments in PrP-CAA and GSS are composed of 3-repeat and 4-repeat Tau isoforms, having a striking similarity to NFTs in Alzheimer disease (AD). In PrP-CAA, Tau filaments are made of both paired helical filaments (PHFs) and straight filaments (SFs), while in GSS only PHFs were found. Mass spectrometry analyses of Tau filaments extracted from PrP-CAA and GSS brains show the presence of post-translational modifications that are comparable to those seen in Tau aggregates from AD. Cryo-EM analysis reveals that the atomic models of the Tau filaments obtained from PrP-CAA and GSS are identical to those of the Tau filaments from AD, and are therefore distinct from those of Pick disease, chronic traumatic encephalopathy, and corticobasal degeneration. Our data support the hypothesis that in the presence of amyloid deposits and regardless of the primary amino acid sequence of the amyloid protein, similar molecular mechanisms are at play in the formation of identical Tau filaments.

Dataset Information

Hingant2014 - Micellar On-Pathway Intermediate in Prion Amyloid Formation

Publications

A micellar on-pathway intermediate step explains the kinetics of prion amyloid formation.

Similar Datasets

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