Ferroptosis is a type of regulated cell death characterized by intracellular accumulation of iron and reactive oxygen species, inhibition of system Xc-, glutathione depletion, nicotinamide adenine dinucleotide phosphate oxidation and lipid peroxidation. Since its discovery and characterization in 2012, many efforts have been made to reveal the underlying mechanisms, modulating compounds, and its involvement in disease pathways. Ferroptosis inducers include erastin, sorafenib, sulfasalazine and glutamate, which, by inhibiting system Xc-, prevent the import of cysteine into the cells. RSL3, statins, Ml162 and Ml210 induce ferroptosis by inhibiting glutathione peroxidase 4 (GPX4), which is responsible for preventing the formation of lipid peroxides, and FIN56 and withaferin trigger GPX4 degradation. On the other side, ferroptosis inhibitors include ferrostatin-1, liproxstatin-1, α-tocopherol, zileuton, FSP1, CoQ10 and BH4, which interrupt the lipid peroxidation cascade. Additionally, deferoxamine, deferiprone and N-acetylcysteine, by targeting other cellular pathways, have also been classified as ferroptosis inhibitors. Increased evidence has established the involvement of ferroptosis in distinct brain diseases, including Alzheimer's, Parkinson's and Huntington's diseases, amyotrophic lateral sclerosis, multiple sclerosis, and Friedreich's ataxia. Thus, a deep understanding of how ferroptosis contributes to these diseases, and how it can be modulated, can open a new window of opportunities for novel therapeutic strategies and targets. Other studies have shown a sensitivity of cancer cells with mutated RAS to ferroptosis induction and that chemotherapeutic agents and ferroptosis inducers synergize in tumor treatment. Thus, it is tempting to consider that ferroptosis may arise as a target mechanistic pathway for the treatment of brain tumors. Therefore, this work provides an up-to-date review on the molecular and cellular mechanisms of ferroptosis and their involvement in brain diseases. In addition, information on the main ferroptosis inducers and inhibitors and their molecular targets is also provided.

The increased bacterial multidrug resistance caused by inappropriate use and overuse of antimicrobials is a global concern. To circumvent this issue, a quest for the development of new active agents has been widely recognized. Some phytochemical products, produced by plants as part of their chemical defense strategies, are regarded as new stimulii to develop novel antimicrobials that are not as vulnerable as current drugs to bacterial resistance mechanisms. In this study, the antimicrobial activity and mode of action of caffeic acid (CAF) and a series of CAF alkyl esters was assessed against Escherichia coli and Staphylococcus aureus, with the aim of analyzing the influence of the alkyl ester side chain length on the activity. Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), changes in physicochemical surface properties and intracellular potassium leakage were used as physiological indices for the antimicrobial mode of action. CAF alkyl esters were found to be effective antimicrobial agents against both bacteria. Their activity was directly dependent on their lipophilicity, which affected bacterial susceptibility, the physicochemical properties of the bacteria and the integrity of the membranes. E. coli was less susceptible than S. aureus to the action of the compounds. Longer alkyl side chains were more effective against the Gram-positive bacterium, while medium length alkyl side chain compounds were more effective against the Gram-negative bacterium. Caffeic acid derivatives are proposed to act as cell permeabilizers, inducing membrane alterations, causing rupture with potassium leakage, particularly on the Gram positive bacterium, and consequent cell death.