Start of funding 01.07.2007

Alzheimer protein structure and dynamics: a combined NMR and Raman spectroscopic approach

PD Dr. Sebastian Schlücker
University of Würzburg
Institute of Physical Chemistry

Assist. Prof. Dr. Tobias S. Ulmer
University of Southern California, Annenberg
Zilkha Neurogenetic Institute, Keck School of Medicine



The protein α-synuclein has been implicated in the molecular chain of events leading to Parkinson’s disease. By itself α-synuclein is largely unfolded as documented by various biophysical techniques such as circular dichroism (CD), Fourier-transform infrared (FT-IR), and nuclear magnetic resonance (NMR) spectroscopy. However, in vivo α-synuclein is predominantly bound to synaptic vesicles via an elongated amphiphilic helix. Cytotoxic soluble as well as insoluble α-synuclein aggregates, which are the hallmarks of Parkinson’s diseases, may arise from both states. Here, we propose to study the interaction of α-synuclein with small molecule inhibitors of filament assembly by NMR and Raman spectroscopy to identify key interaction sites and improve drugs aiming at halting α-synuclein aggregation and, hence, Parkinson’s disease. Additional experiments will be performed on the non-pathogenic β- and γ-synuclein proteins for comparison with α-synuclein.