Abstract
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Exp Neurol. 2023 Dec;370:114538. doi: 10.1016/j.expneurol.2023.114538. Epub 2023 Sep 12.
Effect of ferroptosis on chronic cerebral hypoperfusion in vascular dementia.
Fu P(1), Chen Y(2), Wu M(1), Bao B(1), Yin X(1), Chen Z(3), Zhang M(4).
Author information: (1)Department of Neurology, Clinical Medical School of Jiujiang University, Jiujiang, Jiangxi 332000, China; Jiujiang Clinical Precision Medicine Research Center, Jiujiang, Jiangxi 332000, China. (2)Department of Neurology, Clinical Medical School of Jiujiang University, Jiujiang, Jiangxi 332000, China; Jiujiang Clinical Precision Medicine Research Center, Jiujiang, Jiangxi 332000, China; Department of Neurology, the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330000, China. (3)Department of Neurology, Clinical Medical School of Jiujiang University, Jiujiang, Jiangxi 332000, China; Jiujiang Clinical Precision Medicine Research Center, Jiujiang, Jiangxi 332000, China. Electronic address: zychenjj@jju.edu.cn. (4)School of Basic Medicine, Jiujiang University, Jiujiang, Jiangxi 332000, China. Electronic address: zmqzhang328@163.com.
Vascular dementia (VaD) is the second most prevalent type of dementia after Alzheimer’s disease and is caused by impaired nerve cell function resulting from cerebrovascular disease and vascular risk factors. Chronic cerebral hypoperfusion (CCH) is a common pathological and physiological state that may result from cerebral ischemia and hypoxia, causing widespread diffuse lesions in the brain parenchyma which leads to progressive nerve damage. Transferrin (TF) and transferrin receptor 1 (TfR1), two proteins involved in iron uptake, were upregulated by CCH, whereas ferroprotein (FPN), a protein involved in iron efflux, was downregulated. This process may involve various mechanisms including tau and iron regulatory proteins (IRP). CCH can also exacerbate lipid peroxidation caused by an iron imbalance by inhibiting glutathione peroxidase 4 (Gpx4) synthesis and some Gpx4 independent pathways through cystine/glutamate transporters (system Xc-), ultimately leading to ferroptosis in nerve cells and accelerating the progression of VaD.
Copyright © 2023 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.expneurol.2023.114538 PMID: 37709116 [Indexed for MEDLINE]
Conflict of interest statement: Declaration of Competing Interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled.