Structural basis of membrane disruption and cellular toxicity by {alpha}-synuclein oligomers

Oligomeric species populated during the aggregation process of α-synuclein have been linked to neuronal impairment in Parkinson’s disease and related neurodegenerative disorders. By using solution and solid-state nuclear magnetic resonance techniques in conjunction with other structural methods, we identified the fundamental characteristics that enable toxic α-synuclein oligomers to perturb biological membranes and disrupt cellular function; these include a highly lipophilic element that promotes strong membrane interactions and a structured region that inserts into lipid bilayers and disrupts their integrity. In support of these conclusions, mutations that target the region that promotes strong membrane interactions by α-synuclein oligomers suppressed their toxicity in neuroblastoma cells and primary cortical neurons.

Source: ScienceNOW - December 14, 2017 Category: Science Authors: Fusco, G., Chen, S. W., Williamson, P. T. F., Cascella, R., Perni, M., Jarvis, J. A., Cecchi, C., Vendruscolo, M., Chiti, F., Cremades, N., Ying, L., Dobson, C. M., De Simone, A. Tags: Biochemistry, Neuroscience reports Source Type: news