Mechanism of iron accumulation and its research progress in neurodegenerative diseases
LIU Jiaoru1* YANG Hui2* WANG Haiyan2 XING Yonghua2 TONG Li1 SU Zhanhai2 WU Qiong1
1.Medical Institute of Qinghai University, Qinghai Provincial Key Laboratory of Traditional Chinese Medicine Research for Glucolipid Metabolic Diseases, Qinghai Province, Xining 810016, China;
2.Medical Institute of Qinghai University, Laboratory of Basic and Applied Research on Qinghai-Tibet Plateau Traditional Chinese Medicine Anti-tumor Medicine, Qinghai Province, Xining 810016, China
Abstract:The iron-dependent accumulation associated with lipid peroxides in cells, mitochondrial atrophy, and increased mitochondrial membrane density are the main pathological features of ferroptosis. It is different from the cell necrosis, autophagy, and apoptosis. The mechanism of ferroptosis usually involved with the accumulation of lipids and lipid peroxides, the imbalance of amino acid antioxidant system, and the disorder of iron metabolism. Therefore, ferroptosis is considered as a novel programmed cell death process. The signaling of mevalonic acid, transsulfur, and heat shock protein may play important roles in the ferroptosis process. Existing studies have shown that ferroptosis is strongly associated with the development of some neurodegenerative diseases. But the exact mechanism of this form of cell death has not been fully explored. This review summarizes the latest research development of the role of ferroptosis in neurodegenerative system diseases, and further understanding of ferroptosis may inform future clinical treatment research of neurodegenerative diseases.
刘皎茹1* 杨惠2* 王海燕2 邢永华2 童丽1 苏占海2 吴穹1. 铁死亡的机制及其在神经退行性疾病中的研究进展[J]. 中国医药导报, 2023, 20(22): 38-42.
LIU Jiaoru1* YANG Hui2* WANG Haiyan2 XING Yonghua2 TONG Li1 SU Zhanhai2 WU Qiong1. Mechanism of iron accumulation and its research progress in neurodegenerative diseases. 中国医药导报, 2023, 20(22): 38-42.
[1] Galluzzi L,Bravo-San Pedro JM,Vitale I,et al. Essential versus accessory aspects of cell death:recommendations of the NCCD 2015 [J]. Cell Death Differ,2015,22(1):58-73.
[2] Li J,Cao F,Yin HL,et al. Ferroptosis:past,present and future [J]. Cell Death Dis,2020,11(2):88.
[3] Xie Y,Hou W,Song X,et al. Ferroptosis:process and function [J]. Cell Death Differ,2016,23(3):369-379.
[4] Sun Y,Xia X,Basnet D,et al. Mechanisms of Ferroptosis and Emerging Links to the Pathology of Neurodegenerative Diseases [J]. Front Aging Neurosci,2022,14:904152.
[5] Bridges RJ,Natale NR,Patel SA. System xc- cystine/glutamate antiporter: an update on molecular pharmacology and roles within the CNS [J]. Br J Pharmacol,2012,165(1):20- 34.
[6] Wang L,Liu Y,Du T,et al. ATF3 promotes erastin-induced ferroptosis by suppressing system Xc [J]. Cell Death Differ,2020,27(2):662-675.
[7] Wang K,Zhang Z,Tsai HI,et al. Branched-chain amino acid aminotransferase 2 regulates ferroptotic cell death in cancer cells [J]. Cell Death Differ,2021,28(4):1222-1236.
[8] Zhang X,Yu K,Ma L,et al. Endogenous glutamate determines ferroptosis sensitivity via ADCY10-dependent YAP suppression in lung adenocarcinoma [J]. Theranostics,2021, 11(12):5650-5674.
[9] Andersen JV,Markussen KH,Jakobsen E,et al. Glutamate metabolism and recycling at the excitatory synapse in health and neurodegeneration [J]. Neuropharmacology,2021,196:108719.
[10] Sun Y,Zheng Y,Wang C,et al. Glutathione depletion induces ferroptosis,autophagy,and premature cell senescence in retinal pigment epithelial cells [J]. Cell Death Dis,2018,9(7):753.
[11] Gaschler MM,Stockwell BR. Lipid peroxidation in cell death [J]. Biochem Biophys Res Commun,2017,482(3):419-425.
[12] Liang D,Minikes AM,Jiang X. Ferroptosis at the intersection of lipid metabolism and cellular signaling [J]. Mol Cell,2022,82(12):2215-2227.
[13] Wenzel SE,Tyurina YY,Zhao J,et al. PEBP1 Wardens Ferroptosis by Enabling Lipoxygenase Generation of Lipid Death Signals [J]. Cell,2017,171(3):628-641.e26.
[14] Yang WS,Kim KJ,Gaschler MM,et al. Peroxidation of pol- yunsaturated fatty acids by lipoxygenases drives ferroptosis [J]. Proc Natl Acad Sci U S A,2016,113(34):E4966- 75.
[15] Xie LH,Fefelova N,Pamarthi SH,et al. Molecular Mechanisms of Ferroptosis and Relevance to Cardiovascular Disease [J]. Cells,2022,11(17):2726.
[16] Santana-Codina N,Gikandi A,Mancias JD. The Role of NCOA4-Mediated Ferritinophagy in Ferroptosis [J]. Adv Exp Med Biol,2021,1301:41-57.
[17] Lill R,Hoffmann B,Molik S,et al. The role of mitochondria in cellular iron-sulfur protein biogenesis and iron metabo- lism [J]. Biochim Biophys Acta,2012,1823(9):1491-1508.
[18] Liu J,Kang R,Tang D. Signaling pathways and defense mec- hanisms of ferroptosis [J]. FEBS J,2022,289(22):7038- 7050.
[19] Wei X,Yi X,Zhu XH,et al. Posttranslational Modifications in Ferroptosis [J]. Oxid Med Cell Longev,2020,2020:8832043.
[20] Yuan Y,Zhai Y,Chen J,et al. Kaempferol Ameliorates Oxygen-Glucose Deprivation/Reoxygenation-Induced Neuronal Ferroptosis by Activating Nrf2/SLC7A11/GPX4 Axis [J]. Biomolecules,2021,11(7):923.
[21] Dodson M,Castro-Portuguez R,Zhang DD. NRF2 plays a critical role in mitigating lipid peroxidation and ferroptosis [J]. Redox Biol,2019,23:101107.
[22] Yao Y,Chen Z,Zhang H,et al. Selenium-GPX4 axis protects follicular helper T cells from ferroptosis [J]. Nat Immunol,2021,22(9):1127-1139.
[23] Cao JY,Dixon SJ. Mechanisms of ferroptosis [J]. Cell Mol Life Sci,2016,73(11-12):2195-2209.
[24] Breijyeh Z,Karaman R. Comprehensive Review on Alzhei- mer’s Disease:Causes and Treatment [J]. Molecules,2020, 25(24):5789.
[25] Dusek P,Hofer T,Alexander J,et al. Cerebral Iron Deposition in Neurodegeneration[J]. Biomolecules,2022,12(5):714.
[26] Lane DJR,Metselaar B,Greenough M,et al. Ferroptosis and NRF2:an emerging battlefield in the neurodegeneration of Alzheimer’s disease [J]. Essays Biochem,2021,65(7):925-940.
[27] Liu JL,Fan YG,Yang ZS,et al. Iron and Alzheimer’s Disease:From Pathogenesis to Therapeutic Implications [J]. Front Neurosci,2018,12:632.
[28] Ayton S,Fazlollahi A,Bourgeat P,et al. Cerebral quantitative susceptibility mapping predicts amyloid-β-related cognitive decline [J]. Brain,2017,140(8):2112-2119.
[29] Li J,Li M,Ge Y,et al. β-amyloid protein induces mitophagy-dependent ferroptosis through the CD36/PINK/ PARKIN pathway leading to blood-brain barrier destruction in Alzheimer’s disease [J]. Cell Biosci,2022,12(1):69.
[30] Currais A,Maher P. Functional consequences of age-dependent changes in glutathione status in the brain [J]. Antioxid Redox Signal,2013,19(8):813-822.
[31] Park MW,Cha HW,Kim J,et al. NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer’s diseases [J]. Redox Biol,2021,41:101947.
[32] Hager K,Kenklies M,McAfoose J,et al. Alpha-lipoic acid as a new treatment option for Alzheimer’s disease--a 48 months follow-up analysis [J]. J Neural Transm Suppl,2007(72):189-193.
[33] Kaur D,Behl T,Sehgal A,et al. Decrypting the potential role of α-lipoic acid in Alzheimer’s disease [J]. Life Sci,2021,284:119899.
[34] Williams CT,De Jesus O. Friedreich Ataxia [M]. Treasure Island (FL):StatPearls Publishing,2022.
[35] Campuzano V,Montermini L,Moltò MD,et al. Friedreich’s ataxia:autosomal recessive disease caused by an intronic GAA triplet repeat expansion [J]. Science,1996,271(5254): 1423-1427.
[36] Du J,Zhou Y,Li Y,et al. Identification of Frataxin as a regulator of ferroptosis [J]. Redox Biol,2020,32:101483.
[37] La Rosa P,Petrillo S,Fiorenza MT,et al.Ferroptosis in Friedreich’s Ataxia:A Metal-Induced Neurodegenerative Disease [J]. Biomolecules,2020,10(11):1551.
[38] Feldman EL,Goutman SA,Petri S,et al. Amyotrophic lateral sclerosis [J]. Lancet,2022,400(10360):1363-1380.
[39] Ignjatovi■ A,Stevi■ Z,Lavrni■ D,et al. Inappropriately che- lated iron in the cerebrospinal fluid of amyotrophic lateral sclerosis patients [J]. Amyotroph Lateral Scler,2012,13(4): 357-362.
[40] Moreau C,Danel V,Devedjian JC,et al. Could Conservative Iron Chelation Lead to Neuroprotection in Amyotrophic Lateral Sclerosis [J]. Antioxid Redox Signal,2018,29(8):742-748.
[41] Stein J,Walkenfort B,Cihankaya H,et al. Increased ROS- Dependent Fission of Mitochondria Causes Abnormal Morphology of the Cell Powerhouses in a Murine Model of Amyotrophic Lateral Sclerosis [J]. Oxid Med Cell Longev,2021,2021:6924251.
[42] Zheng Q,Zhao Y,Guo J,et al. Iron overload promotes mitochondrial fragmentation in mesenchymal stromal cells from myelodysplastic syndrome patients through activation of the AMPK/MFF/Drp1 pathway [J]. Cell Death Dis,2018, 9(5):515.
[43] Gouel F,Do Van B,Chou ML,et al. The protective effect of human platelet lysate in models of neurodegenerative disease: involvement of the Akt and MEK pathways [J]. J Tissue Eng Regen Med,2017,11(11):3236-3240.
[44] Stoker TB,Mason SL,Greenland JC,et al. Huntington’s disease:diagnosis and management [J]. Pract Neurol,2022, 22(1):32-41.
[45] Reichert CO,de Freitas FA,Sampaio-Silva J,et al. Ferroptosis Mechanisms Involved in Neurodegenerative Diseases [J]. Int J Mol Sci,2020,21(22):8765.
[46] Skouta R,Dixon SJ,Wang J,et al. Ferrostatins inhibit oxidative lipid damage and cell death in diverse disease models [J]. J Am Chem Soc,2014,136(12):4551-4556.
[47] Simon DK,Tanner CM,Brundin P. Parkinson Disease Epidemiology,Pathology,Genetics,and Pathophysiology [J]. Clin Geriatr Med,2020,36(1):1-12.
[48] Jiang H,Wang J,Rogers J,et al. Brain Iron Metabolism Dysfunction in Parkinson’s Disease [J]. Mol Neurobiol,2017, 54(4):3078-3101.
[49] Mamais A,Kluss JH,Bonet-Ponce L,et al. Mutations in LRRK2 linked to Parkinson disease sequester Rab8a to damaged lysosomes and regulate transferrin-mediated iron uptake in microglia [J]. PLoS Biol,2021,19(12):e3001480.
[50] Du XY,Xie XX,Liu RT. The Role of α-Synuclein Oligomers in Parkinson’s Disease [J]. Int J Mol Sci,2020,21(22):8645.
[51] Sterling JK,Kam TI,Guttha S,et al. Interleukin-6 triggers toxic neuronal iron sequestration in response to pathological α-synuclein [J]. Cell Rep,2022,38(7):110358.
[52] Mahoney-Sánchez L,Bouchaoui H,Ayton S,et al. Ferroptosis and its potential role in the physiopathology of Parkinson’s Disease [J]. Prog Neurobiol,2021,196:101890.
[53] Ma J,Li X,Fan Y,et al. miR-494-3p Promotes Erastin- Induced Ferroptosis by Targeting REST to Activate the Interplay between SP1 and ACSL4 in Parkinson’s Disease [J]. Oxid Med Cell Longev,2022,2022:7671324.
[54] Sun Y,He L,Wang T,et al. Activation of p62-Keap1-Nrf2 Pathway Protects 6-Hydroxydopamine-Induced Ferroptosis in Dopaminergic Cells [J]. Mol Neurobiol,2020,57(11):4628-4641.