Table 2.
Pharmacological inhibition of ferroptosis in the therapy of neurodegenerative diseases (NGDs).
| Compound | Target | Mode of action | NGD | References (PMID) |
|---|---|---|---|---|
| Selenium | GPX4 | GPX4 synthesis | AD |
29974078 27447428 25567069 |
| GSH | GPX4 | Increase GPX4 activity | PD | 28436395 |
| N-acetyl cysteine | GSH and GPX4 | Increases GSH and GPX4 activity | PD, AD |
28499986 30574085 |
| Liproxstatin-1 | Lipid peroxides and GPX4 | Inhibition of lipid peroxidation and restoration of the expression of GPX4 and FSP1 | AD, ALS |
33398092 32985488 |
| Ferrostatin-1 | Lipid peroxides and GPX4 | Inhibition of the production of ROS | PD, ALS |
33398092 34145375 36443440 |
| Vitamin E | Lipid peroxides | Prevents lipid peroxidation and iron accumulation | PD, ALS |
35122944 26400084 34111668 |
| Salidroside | NRF2 | Activation of NRF2/HO1/GPX4 signaling pathway | AD |
36965372 35787281 |
| Quercetin | NRF2 | Activation of NRF2 | PD |
36105483 36501161 |
| β-Hydroxybutyric acid | NRF2 | Activation of NRF2 pathway | PD, AD |
36435477 36118706 37164173 |
| Deferoxamine | Iron | Iron chelation, upregulation of GPX4 and FTH1, and prevention of oxidative stress | AD, ALS |
33646533 35313783 34111668 |
| Deferiprone | Iron | Inhibition of lipid peroxidation | PD, ALS |
31912279 21791473 31202468 18331585 36449420 28469157 |
| Clioquinol | Iron | Iron chelation and activation of AKT/mTOR survival pathway | PD, AD |
32424108 22286308 |
| Salicylaldehyde isonicotinoyl hydrazone | Iron | Iron chelation | ALS | 19158288 |
| Edaravone | FR | FR scavenger that eliminates the generation of hydroxyl radicals and peroxynitrite radicals | AD, ALS |
36333599 32077821 |
| Senegenin | RhoGDIα | Upregulation of GPX4 and downregulation of PEBP1 and ACSL4 | AD |
36068400 35080740 |
| Coenzyme Q10 | FSP1 | Increase FSP1 activity | AD, PD |
29154270 24664227 |
| Eriodictyol | VDR | Activation of the Nrf2/HO-1 signaling pathway | AD | 35093024 |
| (−)-Clausenamide | ALOX5 | Inhibition of the nuclear translocation of ALOX5 | PD, AD |
37121496 20674676 |
NGD Neurodegenerative disease, GPX4 Glutathione peroxidase 4, AD Alzheimer's disease, GSH Glutathione, PD Parkinson's disease, FSP1 Ferroptosis suppressor protein 1, ALS Amyotrophic lateral sclerosis, ROS Reactive oxygen species, NRF2 Nuclear factor erythroid 2-related factor 2, HO1 Heme oxygenase 1, FTH1 Ferritin heavy chain 1, mTOR - Mechanistic target of rapamycin, FR Free radical, RhoGDIα - Rho GDP dissociation inhibitor alpha, PEBP1 Phosphatidylethanolamine-binding protein 1, ACSL4 Acyl-CoA synthetase long-chain family member 4, VDR Vitamin D receptor, ALOX5 5-lipoxygenase.