Rethinking IRPs/IRE system in neurodegenerative disorders: Looking beyond iron metabolism.

Zhengyang Yao, Lin Fu, Fengju Jia, Mingxia Bi, Qian Jiao, Xi Chen, Xixun Du, Hong Jiang

Journal: Ageing research reviews 2022;73():101511

PMID: 34767973

Full Text on Elsevier Science View on PubMed

Abstract

Iron regulatory proteins (IRPs) and iron regulatory element (IRE) systems are well known in the progression of neurodegenerative disorders by regulating iron related proteins. IRPs are also regulated by iron homeostasis. However, an increasing number of studies have suggested a close relationship between the IRPs/IRE system and non-iron-related neurodegenerative disorders. In this paper, we reviewed that the IRPs/IRE system is not only controlled by iron ions, but also regulated by such factors as post-translational modification, oxygen, nitric oxide (NO), heme, interleukin-1 (IL-1), and metal ions. In addition, by regulating the transcription of non-iron related proteins, the IRPs/IRE system functioned in oxidative metabolism, cell cycle regulation, abnormal proteins aggregation, and neuroinflammation. Finally, by emphasizing the multiple regulations of IRPs/IRE system and its potential relationship with non-iron metabolic neurodegenerative disorders, we provided new strategies for disease treatment targeting IRPs/IRE system.

Address: Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines: Physiology, School of Basic Medicine, Medical College, Qingdao University, Qingdao, China.; Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines: Physiology, School of Basic Medicine, Medical College, Qingdao University, Qingdao, China. Electronic address: [email protected].

DOI: 10.1016/j.arr.2021.101511

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MeSH Terms: Homeostasis, Humans, Iron, Iron-Regulatory Proteins, Neurodegenerative Diseases, Neuroinflammatory Diseases