CRMP1 protein complexes modulate polyQ-mediated Htt aggregation and toxicity in neurons [Elektronische Ressource] / von Yacine Bounab

CRMP1 Protein Complexes Modulate PolyQ-Mediated Htt Aggregation and Toxicity in Neurons DISSERTATION zur Erlangung des akademischen Grades doctor rerum naturalium (Dr.rer.nat.) im Fach Biologie eingereicht an der Mathematisch-Naturwissenschaftlichen Fakultät I Humboldt-Universität zu Berlin von Herr Dipl.-Ing. Yacine Bounab Präsident der Humboldt-Universität zu Berlin: Prof.Dr. Christoph Markschies Dekan der Mathematisch-Naturwissenschaftlichen Fakultät I: Prof.Dr. Lutz-Helmut-Schön Gutachter: 1. Prof.Dr. Erich Wanker 2. Prof.Dr. Andreas Herrmann Eingereicht am: 29.Juli 2009 Tag der mündlichen Prüfung: 21. Januar 2010 Abstract Huntington’s disease (HD) is an inherited neurodegenerative disorder characterized by the accumulation of N-terminal polyglutamine (polyQ)-containing huntingtin (Htt) fragments in affected neurons. The mutant Htt (mHtt) protein is ubiquitously expressed but causes specific dysfunction and death of striatal medium-sized spiny neurons (MSNs) (Albin, 1995; Herden, 1995; Sharp, 1995; Trottier, 1995). Several lines of evidence indicate that mHtt misfolding and aggregation is associated with cytotoxicity in HD models and patients (Sanchez, 2003). It is assumed that striatum specific proteins interacting with Htt might play an important role in HD pathogenesis (Ross, 1995; Harjes and Wanker, 2003).