The Role and Mechanisms of Ubiquitin-Proteasome System-Mediated Ferroptosis in Neurological Disorders
Xin Liu1,2 · Wei Wang3 · Qiucheng Nie1,4 · Xinjing Liu1,4 · Lili Sun1,4 · Qiang Ma3 · Jie Zhang1,2 · Yiju Wei1,41 Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117, China
2 Biomedical Sciences College & Shandong Medicinal Biotechnology Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117, China
3 Cancer Biology Institute, Baotou Medical College, Baotou 014010, China
4 School of Life Science, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117, China
Abstract
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 neurological conditions, the UPS plays a significant role in regulating 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 potential drug targets. Further investigation into the mechanisms of UPS-mediated ferroptosis will provide novel insights and strategies for therapeutic interventions and clinical applications in neurological diseases.
Keywords
Ferroptosis; Neurological disorders; Ubiquitin-proteasome system; Iron
