Figure 8Figure 8
Summary of the mechanisms of ferroptosis in ALS and ferroptosis as a therapeutic target for ALS. Riluzole, a glutamate antagonist, alleviates mitochondrial respiratory chain inhibition in ALS by preventing Ca² + overload and suppressing excitotoxic damage to motor neurons. Edaravone (EDA) inhibits ferroptosis under Cys deficiency and Xc − /GPX4 suppression. SPY1 reduces lipid peroxidation (LPO) and inhibits ferroptosis by upregulating the GCH1/BH4 axis and downregulating abnormally elevated TfR1 expression. Within endosomes, Fe³ + is reduced to Fe² + and transported into the cytosol via DMT1, increasing the risk of LIP formation and ferroptosis induction. Conversely, Fpn1 helps maintain intracellular Fe² + homeostasis by exporting excess Fe² + from the cell. ABAH, 4-aminobenzoic acid hydrazide; BH4, tetrahydrobiopterin; Ca² + , calcium ion; DMT1, divalent metal transporter 1; EDA, edaravone; ERK, extracellular signal-regulated kinase; Fer-1, ferrostatin-1; Fe² + /Fe³ + , ferrous/f