biostudies-otherUnknown6Lucian SmithPhysical biology036005Homo sapienshttps://www.ebi.ac.uk/biostudies/studies/MODEL1409100000biostudies-other19411740Audald Lloret i VillasadministratorLucian SmithfalseSneppen2009 - Modeling proteasome dynamics in Parkinson's disease<notes xmlns="http://www.sbml.org/sbml/level2/version4"> <body xmlns="http://www.w3.org/1999/xhtml"> <div class="dc:title">Sneppen2009 - Modeling proteasome dynamics inParkinson's disease</div><div class="dc:bibliographicCitation"> <p>This model is described in the article:</p> <div class="bibo:title"> <a href="http://identifiers.org/pubmed/19411740" title="Access to this publication">Modeling proteasome dynamics in Parkinson's disease.</a> </div> <div class="bibo:authorList">Sneppen K, Lizana L, Jensen MH, Pigolotti S, Otzen D.</div> <div class="bibo:Journal">Phys Biol 2009; 6(3): 036005</div> <p>Abstract:</p> <div class="bibo:abstract"> <p>In Parkinson's disease (PD), there is evidence that alpha-synuclein (alphaSN) aggregation is coupled to dysfunctional or overburdened protein quality control systems, in particular the ubiquitin-proteasome system. Here, we develop a simple dynamical model for the on-going conflict between alphaSN aggregation and the maintenance of a functional proteasome in the healthy cell, based on the premise that proteasomal activity can be titrated out by mature alphaSN fibrils and their protofilament precursors. In the presence of excess proteasomes the cell easily maintains homeostasis. However, when the ratio between the available proteasome and the alphaSN protofilaments is reduced below a threshold level, we predict a collapse of homeostasis and onset of oscillations in the proteasome concentration. Depleted proteasome opens for accumulation of oligomers. Our analysis suggests that the onset of PD is associated with a proteasome population that becomes occupied in periodic degradation of aggregates. This behavior is found to be the general state of a proteasome/chaperone system under pressure, and suggests new interpretations of other diseases where protein aggregation could stress elements of the protein quality control system.</p> </div></div><div class="dc:publisher"> <p>This model is hosted on <a href="http://www.ebi.ac.uk/biomodels/">BioModels Database</a> and identified by: <a href="http://identifiers.org/biomodels.db/BIOMD0000000548">BIOMD0000000548</a>.</p> <p>To cite BioModels Database, please use: <a href="http://identifiers.org/pubmed/20587024" title="Latest BioModels Database publication">BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models</a>.</p></div><div class="dc:license"> <p>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 <a href="http://creativecommons.org/publicdomain/zero/1.0/" title="Access to: CC0 1.0 Universal (CC0 1.0), Public Domain Dedication">CC0 Public Domain Dedication</a> for more information.</p></div></body> </notes>2014-09-10T00:00:00Z2025-07-15T10:01:21.808Z2025-03-29T13:32:16.321ZMODEL1409100000BIOMD000000054819411740MAMO_0000046GO:0043161GO:0070841GO:0000502GO:0043205DOID:143309606BTO:0000142P37840