Comparison of α-Synuclein and Amyloid Beta Membrane Interactions

Abstract

α-synuclein (αSyn) and amyloid beta (1-42) peptide (Aβ) are the main constituents of pathological deposits in the midbrain of individuals affected by Parkinson’s disease and Alzheimer’s disease respectively. Defining the interactions of αSyn and Aβ with membranes is essential for understanding the neurotoxicity caused by mutations and/or overexpression.View Large Image | View Hi-Res Image | Download PowerPoint SlideWe performed a systematic in vitro study of the effects of membrane charge, phase, curvature, defects and lipid unsaturation on αSyn and Aβ binding using model vesicles and proteins labeled with a new solvatochromic fluorescent probe. The probe’s emission spectrum strongly depends on the membrane properties, allowing clear discrimination of the protein bound to vesicles of different composition that enables measurements of the kinetics of αSyn migration between membranes of different compositions [1]. The interaction of αSyn with vesicular membranes is fast and reversible while the membrane binding of Aβ is mainly kinetically controlled and competes with aggregation. By introducing the probe at different positions of αSyn and Aβ we were able to estimate the relative immersion of different protein domains into membrane, and its changes depending on membrane composition and lipid-to-protein ratio.[1] Shvadchak, et al., J. Biol. Chem., (2011).