RT Journal
A1 Stroedicke, Martin
A1 Bounab, Yacine
A1 Strempel, Nadine
A1 Klockmeier, Konrad
A1 Yigit, Sargon
A1 Friedrich, Ralf P.
A1 Chaurasia, Gautam
A1 Li, Shuang
A1 Hesse, Franziska
A1 Riechers, Sean-Patrick
A1 Russ, Jenny
A1 Nicoletti, Cecilia
A1 Boeddrich, Annett
A1 Wiglenda, Thomas
A1 Haenig, Christian
A1 Schnoegl, Sigrid
A1 Fournier, David
A1 Graham, Rona K.
A1 Hayden, Michael R.
A1 Sigrist, Stephan
A1 Bates, Gillian P.
A1 Priller, Josef
A1 Andrade-Navarro, Miguel A.
A1 Futschik, Matthias E.
A1 Wanker, Erich E.
T1 Systematic interaction network filtering identifies CRMP1 as a novel suppressor of huntingtin misfolding and neurotoxicity
JF Genome Research 
JO Genome Research 
YR 2015 
FD April 23 
DO 10.1101/gr.182444.114 
UL http://genome.cshlp.org/content/early/2015/04/03/gr.182444.114.abstract 
AB Assemblies 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.