Ferroptosis is a form of cell death elicited by an imbalance in intracellular iron concentrations,leading to enhanced lipid peroxidation.In neurological disorders,both oxidative stress and mitochondrial damage can con...Ferroptosis is a form of cell death elicited by an imbalance in intracellular iron concentrations,leading to enhanced lipid peroxidation.In neurological disorders,both oxidative stress and mitochondrial damage can contribute to ferroptosis,resulting in nerve cell dysfunction and death.The ubiquitin-proteasome system(UPS)refers to a cellular pathway in which specific proteins are tagged with ubiquitin for recognition and degradation by the proteasome.In neuro-logical conditions,the UPS plays a significant role in regu-lating ferroptosis.In this review,we outline how the UPS regulates iron metabolism,ferroptosis,and their interplay in neurological diseases.In addition,we discuss the future application of small-molecule inhibitors and identify poten-tial drug targets.Further investigation into the mechanisms of UPS-mediated ferroptosis will provide novel insights and strategies for therapeutic interventions and clinical applica-tions in neurological diseases.展开更多
基金supported by the 2024 Talent Project of Shandong First Medical University(045RC200008)the Taishan Scholars Program(tsqn202211225).
文摘Ferroptosis is a form of cell death elicited by an imbalance in intracellular iron concentrations,leading to enhanced lipid peroxidation.In neurological disorders,both oxidative stress and mitochondrial damage can contribute to ferroptosis,resulting in nerve cell dysfunction and death.The ubiquitin-proteasome system(UPS)refers to a cellular pathway in which specific proteins are tagged with ubiquitin for recognition and degradation by the proteasome.In neuro-logical conditions,the UPS plays a significant role in regu-lating ferroptosis.In this review,we outline how the UPS regulates iron metabolism,ferroptosis,and their interplay in neurological diseases.In addition,we discuss the future application of small-molecule inhibitors and identify poten-tial drug targets.Further investigation into the mechanisms of UPS-mediated ferroptosis will provide novel insights and strategies for therapeutic interventions and clinical applica-tions in neurological diseases.
