Table 1 Experimental evidence showing the importance of ferroptosis in neurological disease models.
Neurological disease model | Detection index | Results | Effect of targeting ferroptosis on disease phenotype | References |
|---|---|---|---|---|
3×Tg-AD in mice | WB for protein expressions of FTH1, FPN1, TFR, GPX4, SLC7A11 and ACSL4; colorimetric detections of SOD, MDA, GSH; ICP-MS analysis of iron | FPN1 ↓, GPX4 ↓, SLC7A11 ↓, GSH ↓ TFR ↑, ACSL4 ↑, MDA ↑, iron ↑ | Berberine alleviated cognitive function, improved the memory and mitigated the degree of anxiety and anxiety-like behaviors | |
α-Synuclein preformed fibrils-induced PD in mice | WB for protein expressions of GPX4, FTH1, HO-1 and Nrf2; Prussian blue staining of iron content | FTH1 ↓, HO-1 ↓, GPX4 ↓, Nrf2 ↓, iron ↑ | Melatonin enhanced motor function by reducing neuroinflammatory response and α-syn aggregation | |
PTZ-induced epileptic seizure in mice | DHE staining for ROS level; qPCR for mRNA expressions of PTGS2, RPL8, DPP4 and ACSL4; WB for protein expressions of GPX4, FSP1 and DHODH; TEM for analysis of mitochondria morphology | Mitochondrial volume ↓, mitochondrial membrane density ↑ ACSL4 ↑, ROS ↑ PTGS2 ↑, RPL8 ↑, DPP4 ↑ FSP1 ↑, DHODH ↑ GPX4 ↓ | Fer-1 reduced seizure score and duration and increased seizure latency | |
KA-induced epilepsy seizure in mice | Nissl staining for analysis of neuronal survival; qPCR for mRNA expressions of PTGS2 and Lox | PTGS2 ↑, Lox ↑ viable neurons ↓ | VPA improved neuronal viability | |
FeCl3-induced epilepsy seizure in mice | WB for protein expressions of GPX4, 4-HNE and Alox12/15; qPCR for mRNA expressions of PTGS2 | 4-HNE ↑, Alox12/15 ↑, PTGS2 ↑, GPX4 ↓ | Baicalein resulted in reductions of seizure score, number of seizures and seizure duration | |
Pilo-induced epilepsy seizure in mice | qPCR for mRNA expressions of PTGS2; WB for protein expressions of GPX4 and 4-HNE; TEM for analysis of mitochondria morphology; Colorimetric detections of GSH and MDA | Mitochondrial volume ↓ GPX4 ↓, GSH ↓ PTGS2 ↑, 4-HNE ↑ MDA ↑ | Ferrostatin-1 decreased seizure severity and frequency | |
LiCl and Pilo-induced seizure in rats | TEM for analysis of mitochondria morphology; WB for protein expressions of GPX4 and DMT1 | Mitochondrial crista ↓ GPX4 ↓, DMT1 ↓ | Klotho ameliorated cognitive deficits and hippocampal neuron death | |
p-MCAO model of stroke in mice | TEM for analysis of mitochondria morphology; WB for protein expressions of GPX4, TFR, FTH1, transferrin and SATB1; Colorimetric detections of SOD, MDA and GSH; Perls-DAB staining for iron content of cortical tissue | Number of mitochondrial cristae ↓, mitochondrial volume ↓ membrane rupture FTH1 ↓, SATB1 ↓, GSH ↓ transferrin ↑, TFR ↑, MDA ↑, iron ↑, SOD ↑ | Danhong injection resulted in smaller cerebral infarct volumes and satisfactory neuronal function recovery | |
Brain injury device model-induced TBI in mice | TEM for analysis of mitochondria morphology; WB for protein expressions of SLC7A11 and GPX4 | Mitochondrial membrane density and mitochondrial cristae ↓ GPX4 ↓, SLC7A11 ↓ | Paeoniflorin alleviated brain edema and enhanced both the rotational walking ability and memory | |
Surgery-induced SCI in rats | WB for protein expressions of ACSL4, GPX4 and Alox15; Colorimetric detections of GSH, MDA and iron | ACSL4 ↑, Alox15 ↑ MDA ↑, iron ↑ GPX4 ↓, GSH ↓ | Liproxstatin-1 reduced blood-spinal cord barrier disruption and improved hindlimb locomotion |
