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
Fusco G.;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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
