Research progress on iron death in Parkinson ' s disease

Parkinson ' s disease (PD) is an age-dependent late-onset neurodegenerative disorder characterized by classic motor and non-motor symptoms. At present, the etiology and mechanism of PD are not fully understood, but in addition to the degeneration of dopaminergic neurons in the substantia nigra densa and the abnormal deposition of α-synuclein in their cells, it has been gradually discovered that a variety of new cell death modes are involved in the development of PD, including pyroptosis, autophagy, and iron death. Cell iron death, as a new type of programmed cell death, is overdriven by lipid peroxidation and regulated by iron dependence, which has common pathophysiological features with PD. Cellular iron death is mainly caused by excessive iron deposition, imbalance of amino acid metabolism, lipid peroxidation, and mitochondrial damage, which lead to nerve cell toxicity, and eventually lead to neuronal cell death and loss. Therefore, some related drugs, such as iron chelating agents, iron death inhibitors, and lipophilic antioxidants, can inhibit cell iron death by inhibiting metal ion reaction, reducing iron metabolism imbalance and oxidative stress damage, so as to intervene in the pathogenesis and progression of PD. Based on this, this paper summarized the potential pathogenic mechanism of iron death in PD and the molecular mechanism of selective inhibition of cell iron death in the remission and treatment of PD, laying a foundation for further development of targeted intervention and treatment of iron death. At the same time, studying the mechanism of cell iron death can provide new ideas and directions for future drug development, help improve the quality of life of PD patients, delay the progression of the disease, and provide more possibilities for the treatment and management of PD.