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, 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.
Exp Neurol. 2023 Dec;370:114538. doi: 10.1016/j.expneurol.2023.114538. Epub 2023 Sep 12.
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.
血管性痴呆（VaD）是仅次于阿尔茨海默病的第二大常见痴呆症类型，是由脑血管疾病和血管危险因素导致的神经细胞功能受损引起的。慢性脑灌注不足（CCH）是一种常见的病理和生理状态，可能由脑缺血和缺氧引起，导致脑实质广泛弥漫性损伤，从而导致进行性神经损伤。转铁蛋白（TF）和转铁蛋白受体 1（TfR1）是两种参与铁摄取的蛋白质，在 CCH 中上调，而铁蛋白（FPN）是一种参与铁外排的蛋白质，在 CCH 中下调。这一过程可能涉及多种机制，包括 tau 和铁调节蛋白（IRP）。CCH 还可以通过抑制谷胱甘肽过氧化物酶 4（Gpx4）的合成以及胱氨酸/谷氨酸转运体（system Xc）中的一些 Gpx4 非依赖性途径来加剧铁失衡引起的脂质过氧化，最终导致神经细胞中的铁死亡，并加速 VaD 的进展。
