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The ferroptosis activator RSL-3 and the PI3K/Akt pathway inhibitor LY294002 reversed Neuritins inhibitory effect on ferroptosis, indicating that Neuritin suppresses neuronal ferroptosis via PI3K/Akt pathway activation ( In vitro experiments confirmed that A 25-35 treatment significantly inhibited the activation of the NRF2/SLC7A11/GPX4 signaling pathway in HT22 cells, upregulated the expression of Fe 2+ , TFR1, ACSL4, MDA, and GSSG, and decreased the expression of FTH1, SOD, and GSH, as well as the GSH/GSSG ratio, resulting in dysregulated neuronal iron metabolism, impaired amino acid antioxidant systems, mitochondrial dysfunction, and ferroptosis, which ultimately promoted neuronal injury

[DOI] [PMC free article] [PubMed] [Google Scholar] 180.Wang Y., Qian H

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Oxidative protein damage Proteins are primarily responsible for most functional processes within cells and are thus highly abundant in biological systems, making them important targets of ROS attack