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.

Structural basis of membrane disruption and cellular toxicity by α-synuclein oligomers / Giuliana, Fusco; Chen, Serene W.; Williamson, Philip T. F.; Roberta, Cascella; Michele, Perni; Jarvis, James A.; Cristina, Cecchi; Michele, Vendruscolo; Fabrizio, Chiti; Nunilo, Cremades; Liming, Ying; Dobson, Christopher M.; Alfonso De Simone,. - In: SCIENCE. - ISSN 0036-8075. - STAMPA. - 358:(2017), pp. 1440-1443. [10.1126/science.aan6160]

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

Roberta Cascella;Cristina Cecchi;Fabrizio Chiti;
2017

Abstract

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.
2017
358
1440
1443
Giuliana, Fusco; Chen, Serene W.; Williamson, Philip T. F.; Roberta, Cascella; Michele, Perni; Jarvis, James A.; Cristina, Cecchi; Michele, Vendruscolo; Fabrizio, Chiti; Nunilo, Cremades; Liming, Ying; Dobson, Christopher M.; Alfonso De Simone,
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1106196
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