Repository logo
 
Publication

Systematic interaction network filtering identifies CRMP1 as a novel suppressor of huntingtin misfolding and neurotoxicity

2015-05Journal article Open access
Simple item page
dc.contributor.authorStroedicke, Martin
dc.contributor.authorBounab, Yacine
dc.contributor.authorStrempel, Nadine
dc.contributor.authorKlockmeier, Konrad
dc.contributor.authorYigit, Sargon
dc.contributor.authorFriedrich, Ralf P.
dc.contributor.authorChaurasia, Gautam
dc.contributor.authorLi, Shuang
dc.contributor.authorHesse, Franziska
dc.contributor.authorRiechers, Sean-Patrick
dc.contributor.authorRuss, Jenny
dc.contributor.authorNicoletti, Cecilia
dc.contributor.authorBoeddrich, Annett
dc.contributor.authorWiglenda, Thomas
dc.contributor.authorHaenig, Christian
dc.contributor.authorSchnoegl, Sigrid
dc.contributor.authorFournier, David
dc.contributor.authorGraham, Rona K.
dc.contributor.authorHayden, Michael R.
dc.contributor.authorSigrist, Stephan
dc.contributor.authorBates, Gillian P.
dc.contributor.authorPriller, Josef
dc.contributor.authorAndrade-Navarro, Miguel A.
dc.contributor.authorFutschik, Matthias E.
dc.contributor.authorWanker, Erich E.
dc.date.accessioned2018-12-07T14:53:49Z
dc.date.available2018-12-07T14:53:49Z
dc.date.issued2015-05
dc.description.abstractAssemblies of huntingtin (HTT) fragments with expanded polyglutamine (polyQ) tracts are a pathological hallmark of Huntington's disease (HD). The molecular mechanisms by which these structures are formed and cause neuronal dysfunction and toxicity are poorly understood. Here, we utilized available gene expression data sets of selected brain regions of HD patients and controls for systematic interaction network filtering in order to predict disease-relevant, brain region-specific HTT interaction partners. Starting from a large protein-protein interaction (PPI) data set, a step-by-step computational filtering strategy facilitated the generation of a focused PPI network that directly or indirectly connects 13 proteins potentially dysregulated in HD with the disease protein HTT. This network enabled the discovery of the neuron-specific protein CRMP1 that targets aggregation-prone, N-terminal HTT fragments and suppresses their spontaneous self-assembly into proteotoxic structures in various models of HD. Experimental validation indicates that our network filtering procedure provides a simple but powerful strategy to identify disease-relevant proteins that influence misfolding and aggregation of polyQ disease proteins.
dc.description.sponsorshipDFG [SFB740, 740/2-11, SFB618, 618/3-09, SFB/TRR43 A7]; BMBF(NGFN-Plus) [01GS08169-73, 01GS08150, 01GS08108]; HDSA Coalition for the Cure; EU (EuroSpin) [Health-F2-2009-241498, HEALTH-F2-2009-242167]; Helmholtz Association (MSBN, HelMA) [HA-215]; FCT [IF/00881/2013]
dc.description.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doi10.1101/gr.182444.114
dc.identifier.issn1088-9051
dc.identifier.issn1549-5469
dc.identifier.urihttp://hdl.handle.net/10400.1/11700
dc.language.isoeng
dc.peerreviewedyes
dc.publisherCold Spring Harbor Lab Press, Publications Dept
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectHeat-shock proteins
dc.subjectNeurodegenerative diseases
dc.subjectPolyglutamine proteins
dc.subjectAggregation
dc.subjectBrain
dc.subjectTranscription
dc.subjectExpression
dc.subjectPromotes
dc.subjectNeurons
dc.subjectStress
dc.titleSystematic interaction network filtering identifies CRMP1 as a novel suppressor of huntingtin misfolding and neurotoxicity
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage713
oaire.citation.issue5
oaire.citation.startPage701
oaire.citation.titleGenome Research
oaire.citation.volume25
person.familyNameFutschik
person.givenNameMatthias
person.identifier.ciencia-idA71B-AD01-3501
person.identifier.orcid0000-0002-6245-8071
person.identifier.scopus-author-id14017989400
rcaap.rightsopenAccess
rcaap.typearticle
relation.isAuthorOfPublicationd58f3269-c7e1-4c22-b094-5cfe6750821b
relation.isAuthorOfPublication.latestForDiscoveryd58f3269-c7e1-4c22-b094-5cfe6750821b

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
handle11700.pdf
Size:
1.37 MB
Format:
Adobe Portable Document Format
Download

Collections

FCB2-Artigos (em revistas ou actas indexadas)