Treating incurable non-communicable diseases by targeting iron metabolism and ferroptosis

Both iron metabolism and ferroptosis (an iron-dependent form of programmed cell death) have been connected to the development and progression of many currently incurable non-communicable diseases, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, Huntington's disease, metabolic dysfunction-associated steatohepatitis, heart failure, and both treatment-relapsed and refractory cancers, such as pancreatic ductal adenocarcinoma and triple-negative breast cancer. Thus, understanding the relationship between iron and these diseases can pave the way for the development of novel therapeutic strategies. Here, we summarize the latest evidence supporting the pathological roles of dysregulated iron metabolism and ferroptosis in a wide range of preclinical animal models of these currently incurable non-communicable diseases. We also summarize the feasibility of targeting iron metabolism and ferroptosis for the prevention and treatment of iron- and ferroptosis-related diseases that currently have limited treatment options. In addition, we provide our perspectives on the challenges and promises regarding the translational potential of targeting dysregulated iron metabolism and ferroptosis to treat diseases, highlighting the future roadmap for developing iron- and ferroptosis-targeted therapeutics.