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.