Alpha synuclein aggregation drives ferroptosis: an interplay of iron, calcium and lipid peroxidation.

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 α-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 α-synuclein oligomers into membra

SUBMITTER: Angelova PR 

PROVIDER: S-EPMC7492459 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature