TY  - JOUR
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
Y1  - 2015/05/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 701 
EP  - 713 
DO  - 10.1101/gr.182444.114 
VL  - 25 
IS  - 5 
UR  - http://genome.cshlp.org/content/25/5/701.abstract 
N2  - 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. 
ER  -