4. CONCLUSION AND EXPECTATION
After ferroptosis was defined in 2012, the research on its mechanisms and clinical applications has been a hotspot. The currently known major regulatory mechanisms of ferroptosis involve intracellular lipid metabolism, iron metabolism, GSH-dependent pathway and CoQ10-dependent pathway as stated above. It is possible that certain novel regulators existing in ferroptosis have not been uncovered. And there are still many questions need to be solved regarding the mechanisms of ferroptosis and its relationship with diseases. For example, is there a final biomarker that executes the ferroptotic cell death and what is it? What other roles does mitochondrion play in ferroptosis except that TCA cycle promotes cystine deprivation-induced ferroptosis? Moreover, since the research on ferroptosis mostly focuses on tumor cells, neuronal cells and mouse embryonic fibroblasts, does ferroptosis occur in other cells?
In addition to cancers, ferroptosis has also been reported to be associated with a variety of CNS diseases, and some ferroptosis inhibitors have achieved inspiring results in related animal models. Nonetheless, the role of ferroptosis in CNS diseases needs further elucidation, and currently there is no definitive evidence linking CNS diseases with ferroptosis in long-term animal model studies. There are not enough evidences that ferroptosis is a drug-like target for CNS diseases. Additionally, the existing small molecular regulators of ferroptosis are still limited, and have some disadvantages such as low stability and poor biocompatibility. Therefore, it is urgent to obtain potent ferroptosis inhibitors with good biocompatibility, strong stability and high safety by target-based or cell-based high-throughput screening, structural modification and other methods. The development of such compounds will be an important direction for the prevention and treatments of some human diseases such as CNS diseases.
In conclusion, the research on ferroptosis and its relationship with CNS diseases would be certainly potential for further understanding of the pathogenesis of these diseases and discovery of more effective therapeutic targets, although there are still many unsolved issues in the field. Since no effective therapeutic strategies toward CNS diseases, blockade of ferroptosis may be of value in the treatment of CNS diseases. Further insights into research related to ferroptosis are now likely to emerge rapidly.