RNA m6A甲基化在卒中后认知障碍中的研究进展

doi:10.11958/20230780

天津医药 ›› 2024, Vol. 52 ›› Issue (3): 331-336.doi: 10.11958/20230780

• 综述 • 上一篇

RNA m6A甲基化在卒中后认知障碍中的研究进展

肖雨倩¹(), 孙可心¹, 万俊¹, 陈淑颖¹, 陈丽敏¹, 王岩¹, 白艳杰²^,^△()

1.河南中医药大学（邮编450000）
2.河南中医药大学第一附属医院

收稿日期:2023-05-23 修回日期:2023-08-01 出版日期:2024-03-15 发布日期:2024-03-13
通讯作者: ^△E-mail：baiyj66@126.com
作者简介:肖雨倩（2000），女，硕士在读，主要从事脑卒中后认知障碍研究。E-mail：13569832795@163.com
基金资助:
河南省中医药科学研究专项重点课题(20-21ZY1009);河南省中医药传承与创新人才工程（仲景工程）中医药学科拔尖人才(CZ0237-08);河南省科技攻关计划(222102310529);河南省卫健委国家中医临床研究基地科研专项(2022JDZX005);河南省中医药拔尖人才培养项目专项课题(2022ZYBJ07)

Research progress of RNA m6A methylation in post-stroke cognitive impairment

XIAO Yuqian¹(), SUN Kexin¹, WAN Jun¹, CHEN Shuying¹, CHEN Limin¹, WANG Yan¹, BAI Yanjie²^,^△()

1. Henan University of Chinese Medicine, Zhengzhou 450000, China
2. the First Affiliated Hospital of Henan University of Chinese Medicine

Received:2023-05-23 Revised:2023-08-01 Published:2024-03-15 Online:2024-03-13
Contact: ^△E-mail: baiyj66@126.com

肖雨倩, 孙可心, 万俊, 陈淑颖, 陈丽敏, 王岩, 白艳杰. RNA m6A甲基化在卒中后认知障碍中的研究进展[J]. 天津医药, 2024, 52(3): 331-336.

XIAO Yuqian, SUN Kexin, WAN Jun, CHEN Shuying, CHEN Limin, WANG Yan, BAI Yanjie. Research progress of RNA m6A methylation in post-stroke cognitive impairment[J]. Tianjin Medical Journal, 2024, 52(3): 331-336.

摘要/Abstract

摘要：

卒中后认知障碍（PSCI）主要表现为学习、记忆等方面的障碍。哺乳动物大脑中高度富集的RNA m6A甲基化修饰，参与神经胶质细胞介导的神经炎症。鉴于神经炎症是PSCI神经损伤以及空间和记忆能力下降的主要机制，推测RNA m6A甲基化修饰可调节脑卒中后神经胶质细胞炎症反应，进而改善PSCI。该文就RNA m6A甲基化修饰在PSCI发展中的作用及其调控神经胶质细胞介导的炎症的详细机制进行总结分析，为该领域的研究者提供参考。

关键词: 卒中, 认知障碍, 炎症, 小神经胶质细胞, 星形细胞, m6A甲基化

Abstract:

Post-stroke cognitive impairment (PSCI) is mainly manifested as learning and memory disorders. Highly enriched RNA m6A methylation modification in mammalian brain is involved in glial cell-mediated neuroinflammation. Given that neuroinflammation is the main mechanism for neural damage and spatial and memory impairment of PSCI, it is speculated that RNA m6A methylation modification can regulate the inflammatory response of glial cells after stroke to improve PSCI. This review summarizes and analyzes the role of RNA m6A methylation modification in the development of PSCI and analyzes its detailed mechanism of regulating glial cell-mediated inflammation, which will provide reference for researchers in this field.

Key words: stroke, cognition disorders, inflammation, microglia, astrocytes, m6A methylation

中图分类号:

R743.3

图/表 1

参考文献 49

[1]	LEE K P, CHANG A Y W, SUNG P S. Association between blood pressure,blood pressure variability,and post-stroke cognitive impairment[J]. Biomedicines, 2021, 9(7):773. doi:10.3390/biomedicines9070773.
[2]	RAN Y, SU W, GAO F, et al. Curcumin ameliorates white matter injury after ischemic stroke by inhibiting microglia/macrophage pyroptosis through NF-κB suppression and NLRP3 inflammasome inhibition[J]. Oxid Med Cell Longev, 2021, 2021:1552127. doi:10.1155/2021/1552127.
[3]	LI Q, WEN S, YE W, et al. The potential roles of m6A modification in regulating the inflammatory response in microglia[J]. J Neuroinflammation, 2021, 18(1):149. doi:10.1186/s12974-021-02205-z.
[4]	ZACCARA S, RIES R J, JAFFREY S R. Reading,writing and erasing mRNA methylation[J]. Nat Rev Mol Cell Biol, 2019, 20(10):608-624. doi:10.1038/s41580-019-0168-5.
[5]	YU Z, ZHENG L, GENG Y, et al. FTO alleviates cerebral ischemia/reperfusion-induced neuroinflammation by decreasing cGAS mRNA stability in an m6A-dependent manner[J]. Cell Signal, 2023, 109:110751. doi:10.1016/j.cellsig.2023.110751.
[6]	SCHÖLLER E, WEICHMANN F, TREIBER T, et al. Interactions,localization,and phosphorylation of the m6A generating METTL3-METTL14-WTAP complex[J]. RNA, 2018, 24(4):499-512. doi:10.1261/rna.064063.117.
[7]	AOYAMA T, YAMASHITA S, TOMITA K. Mechanistic insights into m6A modification of U6 snRNA by human METTL16[J]. Nucleic Acids Res, 2020, 48(9):5157-5168. doi:10.1093/nar/gkaa227.
[8]	ZOU J, LIU H, TAN W, et al. Dynamic regulation and key roles of ribonucleic acid methylation[J]. Front Cell Neurosci, 2022, 16:1058083. doi:10.3389/fncel.2022.1058083.
[9]	SPYCHALA A, RÜTHER U. FTO affects hippocampal function by regulation of BDNF processing[J]. PloS One, 2019, 14(2):e0211937. doi:10.1371/journal.pone.0211937.
[10]	DU T, LI G, YANG J, et al. RNA demethylase Alkbh5 is widely expressed in neurons and decreased during brain development[J]. Brain Res Bull, 2020, 163:150-159. doi:10.1016/j.brainresbull.2020.07.018.
[11]	SHI R, YING S, LI Y, et al. Linking the YTH domain to cancer:the importance of YTH family proteins in epigenetics[J]. Cell Death Dis, 2021, 12(4):346. doi:10.1038/s41419-021-03625-8.
[12]	SUN C Y, CAO D, DU B B, et al. The role of insulin-like growth factor 2 mRNA-binding proteins(IGF2BPs)as m(6)A readers in cancer[J]. Int J Biol Sci, 2022, 18(7):2744-2758. doi:10.7150/ijbs.70458.
[13]	CHOE J, LIN S, ZHANG W, et al. mRNA circularization by METTL3-eIF3h enhances translation and promotes oncogenesis[J]. Nature, 2018, 561(7724):556-560. doi:10.1038/s41586-018-0538-8.
[14]	LI X, AN P, HAN F, et al. Silencing of YTHDF1 attenuates cerebral stroke by inducing PTEN degradation and activating the PTEN/AKT/mTOR pathway[J]. Mol Biotechnol, 2022, 65(5):822-832. doi:10.1007/s12033-022-00575-0.
[15]	SI W, LI Y, YE S, et al. Methyltransferase 3 mediated miRNA m6A methylation promotes stress granule formation in the early stage of acute ischemic stroke[J]. Front Mol Neurosci, 2020, 13:103. doi:10.3389/fnmol.2020.00103.
[16]	LIU Y, YAN Z, REN Y, et al. Electroacupuncture inhibits hippocampal neuronal apoptosis and improves cognitive dysfunction in mice with vascular dementia via the JNK signaling pathway[J]. Acupunct Med, 2022:9645284221136878. doi:10.1177/09645284221136878.
[17]	XU K, MO Y, LI D, et al. N(6)-methyladenosine demethylases Alkbh5/Fto regulate cerebral ischemia-reperfusion injury[J]. Ther Adv Chronic Dis, 2020, 11:2040622320916024. doi:10.1177/2040622320916024.
[18]	HOU L, LI S, LI S, et al. FTO inhibits oxidative stress by mediating m6A demethylation of Nrf2 to alleviate cerebral ischemia/reperfusion injury[J]. J Physiol Biochem, 2023, 79(1):133-146. doi:10.1007/s13105-022-00929-x.
[19]	WANG Q S, XIAO R J, PENG J, et al. Bone marrow mesenchymal stem cell-derived exosomal KLF4 alleviated ischemic stroke through inhibiting N6-Methyladenosine modification level of Drp1 by targeting lncRNA-ZFAS1[J]. Mol Neurobiol, 2023, 60(7):3945-3962. doi:10.1007/s12035-023-03301-2.
[20]	LI L, ZANG L, ZHANG F, et al. Fat mass and obesity-associated(FTO)protein regulates adult neurogenesis[J]. Hum Mol Genet, 2017, 26(13):2398-2411. doi:10.1093/hmg/ddx128.
[21]	ZHUANG M, LI X, ZHU J, et al. The m6A reader YTHDF1 regulates axon guidance through translational control of Robo3.1 expression[J]. Nucleic Acids Res, 2019, 47(9):4765-4777. doi:10.1093/nar/gkz157.
[22]	SHI H, ZHANG X, WENG Y L, et al. m(6)A facilitates hippocampus-dependent learning and memory through YTHDF1[J]. Nature, 2018, 563(7730):249-253. doi:10.1038/s41586-018-0666-1.
[23]	CHEN J, ZHANG Y C, HUANG C, et al.m(6)A regulates neurogenesis and neuronal development by modulating histone methyltransferase Ezh2[J]. Genomics Proteomics Bioinformatics, 2019, 17(2):154-168. doi:10.1016/j.gpb.2018.12.007.
[24]	XU S, LI Y, CHEN J P, et al. Oxygen glucose deprivation/re-oxygenation-induced neuronal cell death is associated with Lnc-D63785 m6A methylation and miR-422a accumulation[J]. Cell Death Dis, 2020, 11(9):816. doi:10.1038/s41419-020-03021-8.
[25]	SUN P, MA F, XU Y, et al. Genetic deletion of endothelial microRNA-15a/16-1 promotes cerebral angiogenesis and neurological recovery in ischemic stroke through Src signaling pathway[J]. J Cereb Blood Flow Metab, 2021, 41(10):2725-2742. doi:10.1177/0271678x211010351.
[26]	MATHIYALAGAN P, ADAMIAK M, MAYOURIAN J, et al.FTO-dependent N(6)-methyladenosine regulates cardiac function during remodeling and repair[J]. Circulation, 2019, 139(4):518-532. doi:10.1161/circulationaha.118.033794.
[27]	YAO M D, JIANG Q, MA Y, et al. Role of METTL3-dependent N(6)-methyladenosine mRNA modification in the promotion of angiogenesis[J]. Mol Ther, 2020, 28(10):2191-2202. doi:10.1016/j.ymthe.2020.07.022.
[28]	LI B, XI W, BAI Y, et al.FTO-dependent m(6)A modification of Plpp3 in circSCMH1-regulated vascular repair and functional recovery following stroke[J]. Nat Commun, 2023, 14(1):489. doi:10.1038/s41467-023-36008-y.
[29]	LIANG E, XIAO S, ZHAO C, et al. M6A modification promotes blood-brain barrier breakdown during cerebral ischemia/reperfusion injury through increasing matrix metalloproteinase 3 expression[J]. Heliyon, 2023, 9(6):e16905. doi:10.1016/j.heliyon.2023.e16905.
[30]	LI S, HU W, GONG S, et al. The role of PRRC2B in cerebral vascular remodeling under acute hypoxia in mice[J]. Adv Sci(Weinh), 2023:e2300892. doi:10.1002/advs.202300892.
[31]	ZHANG X, YUAN M, YANG S, et al. Enriched environment improves post-stroke cognitive impairment and inhibits neuroinflammation and oxidative stress by activating Nrf2-ARE pathway[J]. Int J Neurosci, 2021, 131(7):641-649. doi:10.1080/00207454.2020.1797722.
[32]	ZHU L, LIU S, LIAO F, et al. Comprehensive analysis of blood-based m6A methylation in human ischemic stroke[J]. Mol Neurobiol, 2023, 60(2):431-446. doi:10.1007/s12035-022-03064-2.
[33]	CHOKKALLA A K, MEHTA S L, KIM T, et al. Transient focal ischemia significantly alters the m(6)A epitranscriptomic tagging of RNAs in the brain[J]. Stroke, 2019, 50(10):2912-2921. doi:10.1161/strokeaha.119.026433.
[34]	HOSHINO K, HASEGAWA K, KAMIYA H, et al. Synapse-specific effects of IL-1β on long-term potentiation in the mouse hippocampus[J]. Biomed Res, 2017, 38(3):183-188. doi:10.2220/biomedres.38.183.
[35]	AL MAMUN A, CHAUHAN A, QI S, et al. Microglial IRF5-IRF4 regulatory axis regulates neuroinflammation after cerebral ischemia and impacts stroke outcomes[J]. Proc Natl Acad Sci U S A, 2020, 117(3):1742-1752. doi:10.1073/pnas.1914742117.
[36]	WEN L, SUN W, XIA D, et al. The m6A methyltransferase METTL3 promotes LPS-induced microglia inflammation through TRAF6/NF-κB pathway[J]. Neuroreport, 2022, 33(6):243-251. doi:10.1097/wnr.0000000000001550.
[37]	DING L, WU H, WANG Y, et al. m6A reader Igf2bp1 regulates the inflammatory responses of microglia by stabilizing Gbp11 and Cp mRNAs[J]. Front Immunol, 2022, 13:872252. doi:10.3389/fimmu.2022.872252.
[38]	ZHOU H, XU Z, LIAO X, et al. Low expression of YTH domain-containing 1 promotes microglial M1 polarization by reducing the stability of sirtuin 1 mRNA[J]. Front Cell Neurosci, 2021, 15:774305. doi:10.3389/fncel.2021.774305.
[39]	ZHENG L, TANG X, LU M, et al. microRNA-421-3p prevents inflammatory response in cerebral ischemia/reperfusion injury through targeting m6A reader YTHDF1 to inhibit p65 mRNA translation[J]. Int Immunopharmacol, 2020, 88:106937. doi:10.1016/j.intimp.2020.106937.
[40]	TAN C, WU Q, WANG H, et al. Dysbiosis of gut microbiota and short-chain fatty acids in acute ischemic stroke and the subsequent risk for poor functional outcomes[J]. JPEN J Parenter Enteral Nutr, 2021, 45(3):518-529. doi:10.1002/jpen.1861.
[41]	LIAO S, WU J, LIU R, et al. A novel compound DBZ ameliorates neuroinflammation in LPS-stimulated microglia and ischemic stroke rats: role of Akt(Ser473)/GSK3β(Ser9)-mediated Nrf2 activation[J]. Redox Biol, 2020, 36:101644. doi:10.1016/j.redox.2020.101644.
[42]	QI L, HU H, WANG Y, et al. New insights into the central sympathetic hyperactivity post-myocardial infarction: roles of METTL3-mediated m(6)A methylation[J]. J Cell Mol Med, 2022, 26(4):1264-1280. doi:10.1111/jcmm.17183.
[43]	HU W, XIE H, ZENG Y, et al. N6-methyladenosine participates in mouse hippocampus neurodegeneration via PD-1/PD-L1 pathway[J]. Front Neurosci, 2023, 17:1145092. doi:10.3389/fnins.2023.1145092.
[44]	JIANG Z, SHI L, HUANG H, et al. Downregulated FTO promotes microRNA-155-mediated inflammatory response in cerebral ischemia/reperfusion injury[J]. Neuroscience, 2023: 526:305-313. doi:10.1016/j.neuroscience.2023.07.012.
[45]	LIU Q, BHUIYAN M I H, LIU R, et al. Attenuating vascular stenosis-induced astrogliosis preserves white matter integrity and cognitive function[J]. J Neuroinflammation, 2021, 18(1):187. doi:10.1186/s12974-021-02234-8.
[46]	COCKOVA Z, HONC O, TELENSKY P, et al. Streptozotocin-induced astrocyte mitochondrial dysfunction is ameliorated by FTO inhibitor MO-I-500[J]. ACS Chem Neurosci, 2021, 12(20):3818-3828. doi:10.1021/acschemneuro.1c00063.
[47]	HUANG R, ZHANG Y, BAI Y, et al. N(6)-methyladenosine modification of fatty acid amide hydrolase messenger RNA in circular RNA STAG1-regulated astrocyte dysfunction and depressive-like behaviors[J]. Biol Psychiatry, 2020, 88(5):392-404. doi:10.1016/j.biopsych.2020.02.018.
[48]	LI Z, MONIRUZZAMAN M, DASTGHEYB R M, et al. Astrocytes deliver CK1 to neurons via extracellular vesicles in response to inflammation promoting the translation and amyloidogenic processing of APP[J]. J Extracell Vesicles, 2020, 10(2):e12035. doi:10.1002/jev2.12035.
[49]	OUYANG F, JIANG Z, CHEN X, et al. Is cerebral amyloid-β deposition related to post-stroke cognitive impairment?[J]. Transl Stroke Res, 2021, 12(6):946-957. doi:10.1007/s12975-021-00921-5.

RNA m6A甲基化在卒中后认知障碍中的研究进展

Research progress of RNA m6A methylation in post-stroke cognitive impairment

引用本文

RichHTML

PDF (PC)

可视化

摘要/Abstract

使用本文

图/表 1

参考文献 49

相关文章 15

编辑推荐

Metrics

本文评价

[1]	陈晶晶, 农章嵩, 谭良源, 杨培培, 梁英业, 唐宏亮, 王开龙. 小胶质细胞极化在神经病理性疼痛中作用研究进展[J]. 天津医药, 2024, 52(9): 1000-1003.
[2]	范慧慧, 任玉梅, 田新磊, 张凯, 李晓丽. 止咳平喘方对支气管哮喘小鼠气道炎症及TLR4/TRAF6/NF-κB通路的影响[J]. 天津医药, 2024, 52(9): 924-929.
[3]	贾维宁, 鲍亚玲, 雷慧, 殷晓宁. 夏枯草提取物对脓毒症小鼠炎症反应和腹腔巨噬细胞的影响[J]. 天津医药, 2024, 52(9): 930-935.
[4]	郑继青, 龙耀斌, 徐金. 辣椒素联合重复经颅磁刺激用于脑卒中后吞咽障碍患者的疗效观察[J]. 天津医药, 2024, 52(9): 950-953.
[5]	焦爱菊, 任宝龙, 张春花, 李文瑞, 赵玮婧. NIHSS评分联合血清BDNF、IL-6对脑卒中后抑郁的预测价值[J]. 天津医药, 2024, 52(9): 963-966.
[6]	刘斌, 杨龙, 李文莉, 邵宁宁, 董津睿. 小胶质细胞铁死亡在烟雾吸入性脑损伤中的作用机制探讨[J]. 天津医药, 2024, 52(8): 791-797.
[7]	吴波, 朱卓农, 郑丽娟, 陈俊如. 苦参碱对特应性皮炎炎症、氧化应激和伤口愈合的影响[J]. 天津医药, 2024, 52(6): 566-571.
[8]	袁满, 冯子瀚, 谢敏, 王柏军. 大黄素对骨关节炎模型小鼠痛觉行为的调节机制[J]. 天津医药, 2024, 52(6): 572-577.
[9]	蒋韬, 程红艳, 吴琼. 棕矢车菊素调节SDF-1α/CXCR4信号通路对妊娠糖尿病大鼠炎症反应的影响[J]. 天津医药, 2024, 52(6): 594-598.
[10]	薛晶, 元小冬, 邢爱君, 王连辉, 马倩, 符永山, 张萍淑. 急性缺血性脑卒中患者睡眠-觉醒生物节律变化与预后的关系研究[J]. 天津医药, 2024, 52(6): 614-619.
[11]	钱洪春, 张萍淑, 元小冬, 袁建新, 曹凌云, 段丽琴. 卒中伴阻塞性睡眠呼吸暂停患者认知功能损害与睡眠参数的关系[J]. 天津医药, 2024, 52(6): 619-624.
[12]	霍晶辰, 王悦, 李华, 邱嵘, 苏景伟, 王卓凡, 杨洁. 系统免疫炎症指数对根治性放疗Ⅲ期肺鳞癌患者长期生存的预测价值[J]. 天津医药, 2024, 52(6): 634-638.
[13]	韩琴, 韩秀丽, 陈伟然. 老年脑卒中患者康复治疗后抑郁障碍的影响因素分析[J]. 天津医药, 2024, 52(6): 639-642.
[14]	慕静然, 骆延, 梁璇, 徐陶, 曾俊伟, 刘晓红. 补体系统激活参与阿尔茨海默病的研究进展[J]. 天津医药, 2024, 52(6): 663-668.
[15]	张丽红, 李瑞青, 王艺莹, 梅紧紧, 苏凯奇, 顾昌宇, 黄梦玲. 督脉电针调控胱氨酸/谷氨酸反向转运体改善脑卒中后肢体痉挛的作用机制[J]. 天津医药, 2024, 52(5): 463-468.