DC Field | Value | Language |
---|---|---|
dc.contributor.author | Angelova, Plamena R. | ko |
dc.contributor.author | Choil, Minee L. | ko |
dc.contributor.author | Berezhnov, Alexey, V | ko |
dc.contributor.author | Horrocks, Mathew H. | ko |
dc.contributor.author | Hughes, Craig D. | ko |
dc.contributor.author | De, Suman | ko |
dc.contributor.author | Rodrigues, Margarida | ko |
dc.contributor.author | Yapom, Ratsuda | ko |
dc.contributor.author | Little, Daniel | ko |
dc.contributor.author | Dolt, Karamjit S. | ko |
dc.contributor.author | Kunath, Tilo | ko |
dc.contributor.author | Devine, Michael J. | ko |
dc.contributor.author | Gissen, Paul | ko |
dc.contributor.author | Shchepinov, Mikhail S. | ko |
dc.contributor.author | Sylantyev, Sergiy | ko |
dc.contributor.author | Pavlov, Evgeny, V | ko |
dc.contributor.author | Klenerman, David | ko |
dc.contributor.author | Abramov, Andrey Y. | ko |
dc.contributor.author | Gandhi, Sonia | ko |
dc.date.accessioned | 2023-02-06T02:00:24Z | - |
dc.date.available | 2023-02-06T02:00:24Z | - |
dc.date.created | 2023-02-06 | - |
dc.date.created | 2023-02-06 | - |
dc.date.issued | 2020-10 | - |
dc.identifier.citation | CELL DEATH AND DIFFERENTIATION, v.27, no.10, pp.2781 - 2796 | - |
dc.identifier.issn | 1350-9047 | - |
dc.identifier.uri | http://hdl.handle.net/10203/305023 | - |
dc.description.abstract | Protein aggregation and abnormal lipid homeostasis are both implicated in neurodegeneration through unknown mechanisms. Here we demonstrate that aggregate-membrane interaction is critical to induce a form of cell death called ferroptosis. Importantly, the aggregate-membrane interaction that drives ferroptosis depends both on the conformational structure of the aggregate, as well as the oxidation state of the lipid membrane. We generated human stem cell-derived models of synucleinopathy, characterized by the intracellular formation of alpha-synuclein aggregates that bind to membranes. In human iPSC-derived neurons with SNCA triplication, physiological concentrations of glutamate and dopamine induce abnormal calcium signaling owing to the incorporation of excess alpha-synuclein oligomers into membranes, leading to altered membrane conductance and abnormal calcium influx. alpha-synuclein oligomers further induce lipid peroxidation. Targeted inhibition of lipid peroxidation prevents the aggregate-membrane interaction, abolishes aberrant calcium fluxes, and restores physiological calcium signaling. Inhibition of lipid peroxidation, and reduction of iron-dependent accumulation of free radicals, further prevents oligomer-induced toxicity in human neurons. In summary, we report that peroxidation of polyunsaturated fatty acids underlies the incorporation of beta-sheet-rich aggregates into the membranes, and that additionally induces neuronal death. This suggests a role for ferroptosis in Parkinson's disease, and highlights a new mechanism by which lipid peroxidation causes cell death. | - |
dc.language | English | - |
dc.publisher | NATURE PUBLISHING GROUP | - |
dc.title | Alpha synuclein aggregation drives ferroptosis: an interplay of iron, calcium and lipid peroxidation | - |
dc.type | Article | - |
dc.identifier.wosid | 000529005700001 | - |
dc.identifier.scopusid | 2-s2.0-85084117668 | - |
dc.type.rims | ART | - |
dc.citation.volume | 27 | - |
dc.citation.issue | 10 | - |
dc.citation.beginningpage | 2781 | - |
dc.citation.endingpage | 2796 | - |
dc.citation.publicationname | CELL DEATH AND DIFFERENTIATION | - |
dc.identifier.doi | 10.1038/s41418-020-0542-z | - |
dc.contributor.localauthor | Choil, Minee L. | - |
dc.contributor.nonIdAuthor | Angelova, Plamena R. | - |
dc.contributor.nonIdAuthor | Berezhnov, Alexey, V | - |
dc.contributor.nonIdAuthor | Horrocks, Mathew H. | - |
dc.contributor.nonIdAuthor | Hughes, Craig D. | - |
dc.contributor.nonIdAuthor | De, Suman | - |
dc.contributor.nonIdAuthor | Rodrigues, Margarida | - |
dc.contributor.nonIdAuthor | Yapom, Ratsuda | - |
dc.contributor.nonIdAuthor | Little, Daniel | - |
dc.contributor.nonIdAuthor | Dolt, Karamjit S. | - |
dc.contributor.nonIdAuthor | Kunath, Tilo | - |
dc.contributor.nonIdAuthor | Devine, Michael J. | - |
dc.contributor.nonIdAuthor | Gissen, Paul | - |
dc.contributor.nonIdAuthor | Shchepinov, Mikhail S. | - |
dc.contributor.nonIdAuthor | Sylantyev, Sergiy | - |
dc.contributor.nonIdAuthor | Pavlov, Evgeny, V | - |
dc.contributor.nonIdAuthor | Klenerman, David | - |
dc.contributor.nonIdAuthor | Abramov, Andrey Y. | - |
dc.contributor.nonIdAuthor | Gandhi, Sonia | - |
dc.description.isOpenAccess | N | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | REGULATED CELL-DEATH | - |
dc.subject.keywordPlus | PARKINSONS-DISEASE | - |
dc.subject.keywordPlus | LEWY BODIES | - |
dc.subject.keywordPlus | CA2+ INFLUX | - |
dc.subject.keywordPlus | OLIGOMERS | - |
dc.subject.keywordPlus | ASSOCIATION | - |
dc.subject.keywordPlus | ASTROCYTES | - |
dc.subject.keywordPlus | MUTATION | - |
dc.subject.keywordPlus | FORMS | - |
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