Structural basis of membrane disruption and cellular toxicity by α-synuclein oligomers

• DOI: 10.1126/science.aan6160
• Publication Date: 2017-12-14T18:50:52Z
• Authors: Giuliana Fusco; Serene W. Chen; Philip T. F. Will...; Roberta Cascella; Michele Perni; James A. Jarvis; Cristina Cecchi; Michele Vendruscolo; Fabrizio Chiti; Nunilo Cremades; Liming Ying; Christopher M. Do...; Alfonso De Simone
• Keywords: 570; General Science & Technology; Nuclear Magnetic Resonance; Lipid Bilayers; 610; Protein Aggregation, Pathological; Cell Line; FIBRIL; 03 medical and health sciences; PARKINSONS-DISEASE; Pathological; Cell Line, Tumor; BINDING; Cell Line, Tumor; Cell Membrane; Cerebral Cortex; Humans; Lipid Bilayers; Mutation; Neurons; Nuclear Magnetic Resonance, Biomolecular; Parkinson Disease; Protein Aggregation, Pathological; alpha-Synuclein; Humans; α-synuclein oligomers, Parkinson's disease, neuronal toxicity; Nuclear Magnetic Resonance, Biomolecular; Cerebral Cortex; Neurons; 0303 health sciences; Science & Technology; Tumor; Cell Membrane; Parkinson Disease; AGGREGATION; Protein Aggregation; 3. Good health; Multidisciplinary Sciences; STATES; NMR-SPECTROSCOPY; Mutation; alpha-Synuclein; Science & Technology - Other Topics; Biomolecular

A structural look at α-synuclein oligomers

Fibrillar aggregates of the protein α-synuclein (αS) are the major constituents of Lewy bodies in Parkinson's disease. However, small oligomers that accumulate during the process of fibril formation are thought to cause the neuronal toxicity associated with the onset and progression of Parkinson's disease. Little is known about the detailed structural properties of αS oligomers and the molecular mechanisms that lead to their toxicity. Fusco et al. report the structural characterization of two forms of αS oligomers, which elucidates the fundamental structural elements giving rise to neuronal toxicity.

Science , this issue p. 1440