Mitochondrial iron dyshomeostasis and its potential as a therapeutic target for Parkinson's disease.

Zhixin Xiao, Xiaoya Wang, Xuening Pan, Junxia Xie, Huamin Xu

Journal: Experimental neurology 2024;372():114614

PMID: 38007207

Full Text on Elsevier Science View on PubMed

Abstract

Abnormal iron accumulation has been implicated in the etiology of Parkinson's disease (PD). Understanding how iron damages dopaminergic neurons in the substantia nigra (SN) of PD is particularly important for developing targeted neurotherapeutic strategies for the disease. However, it is still not fully understood how excess iron contributes to the neurodegeneration of dopaminergic neurons in PD. There has been increased attention on mitochondrial iron dyshomeostasis, iron-induced mitochondrial dysfunction and ferroptosis in PD. Therefore, this review begins with a brief introduction to describe cellular iron metabolism and the dysregulation of iron metabolism in PD. Then we provide an update on how iron is delivered to mitochondria and induces the damage of dopaminergic neurons in PD. In addition, we also summarize new research progress on iron-dependent ferroptosis in PD and mitochondria-localized proteins involved in ferroptosis. This will provide new insight into potential therapeutic strategies targeting mitochondrial iron dysfunction.

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

DOI: 10.1016/j.expneurol.2023.114614

Link outs

Free resources

Medical:

https://medlineplus.gov/parkinsonsdisease.html

Subscription / membership required

Full Text Sources:

MeSH Terms: Humans, Parkinson Disease, Iron, Mitochondria, Substantia Nigra, Dopaminergic Neurons