Oligomeric species populated during the aggregation process of a-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 a-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 a-synuclein oligomers suppressed their toxicity in neuroblastoma cells and primary cortical neurons.

Structural basis of membrane disruption and cellular toxicity by a-synuclein oligomers / 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.. - In: SCIENCE. - ISSN 0036-8075. - 358:6369(2017), pp. 1440-1443. [10.1126/science.aan6160]

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

De Simone A.
2017

Abstract

Oligomeric species populated during the aggregation process of a-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 a-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 a-synuclein oligomers suppressed their toxicity in neuroblastoma cells and primary cortical neurons.
2017
Structural basis of membrane disruption and cellular toxicity by a-synuclein oligomers / 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.. - In: SCIENCE. - ISSN 0036-8075. - 358:6369(2017), pp. 1440-1443. [10.1126/science.aan6160]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/838335
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