The role of microglia in neurodegenerative diseases: from the perspective of ferroptosis.

Abstract

Iron plays a pivotal role in numerous fundamental biological processes in the brain. Among the various cell types in the central nervous system, microglia are recognized as the most proficient cells in accumulating and storing iron. Nonetheless, iron overload can induce inflammatory phenotype of microglia, leading to the production of proinflammatory cytokines and contributing to neurodegeneration. A growing body of evidence shows that disturbances in iron homeostasis in microglia is associated with a range of neurodegenerative disorders. Recent research has revealed that microglia are highly sensitive to ferroptosis, a form of iron-dependent cell death. How iron overload influences microglial function? Whether disbiosis in iron metabolism and ferroptosis in microglia are involved in neurodegenerative disorders and the underlying mechanisms remain to be elucidated. In this review we focus on the recent advances in research on microglial iron metabolism as well as ferroptosis in microglia. Meanwhile, we provide a comprehensive overview of the involvement of microglial ferroptosis in neurodegenerative disorders from the perspective of crosstalk between microglia and neuron, with a focus on Alzheimer's disease and Parkinson's disease.