m 6 A Modification and its Role in Neural Development and Neurological Diseases DOI
Wan Xin, Yiling Ge, Siyi Xu

et al.

Epigenomics, Journal Year: 2023, Volume and Issue: 15(16), P. 819 - 833

Published: Aug. 1, 2023

N6-methyladenosine (m6A) methylation, the most prevalent post-transcriptional modification in eukaryotes, represents a highly dynamic and reversible process that is regulated by m6A methyltransferases, demethylases RNA-binding proteins during RNA metabolism, which affects function. Notably, significantly enriched brain exerts regulatory roles neurogenesis neurodevelopment through various mechanisms, further influencing occurrence progression of neurological disorders. This study systematically summarizes discusses latest findings on common regulators, examining their expression, function mechanisms diseases. Additionally, we explore potential diagnosing treating disorders, aiming to provide new insights into molecular therapeutic strategies for

Language: Английский

Role of N6-methyladenosine modification in central nervous system diseases and related therapeutic agents DOI Creative Commons
Junya Lv, Lijuan Xing, Xin Zhong

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 162, P. 114583 - 114583

Published: March 28, 2023

N6-methyladenosine (m6A) is a ubiquitous mRNA modification in eukaryotes. m6A occurs through the action of methyltransferases, demethylases, and methylation-binding proteins. methylation RNA associated with various neurological disorders, including Alzheimer's disease (AD), Parkinson's (PD), depression, cerebral apoplexy, brain injury, epilepsy, arteriovenous malformations, glioma. Furthermore, recent studies report that m6A-related drugs have attracted considerable concerns therapeutic areas disorders. Here, we mainly summarized role diseases potential drugs. The aim this review expected to be useful systematically assess as new biomarker develop innovative modulators for amelioration treatment

Language: Английский

Citations

24
WTAP participates in neuronal damage by protein translation of NLRP3 in an m6A-YTHDF1-dependent manner after traumatic brain injury DOI Creative Commons
Yuhua Chen,

Tianlin Long,

Junhui Chen

et al.

International Journal of Surgery, Journal Year: 2024, Volume and Issue: 110(9), P. 5396 - 5408

Published: June 14, 2024

Background Traumatic brain injury (TBI) is a common complication of acute and severe neurosurgery. Remodeling N6-methyladenosine (m6A) stabilization may be an attractive treatment option for neurological dysfunction after TBI. In the present study, authors explored epigenetic methylation RNA-mediated NLRP3 inflammasome activation Methods Neurological dysfunction, histopathology, associated molecules were examined in conditional knockout (CKO) WTAP [flox/flox, Camk2a-cre] , flox/flox pAAV-U6-shRNA-YTHDF1-transfected mice. Primary neurons used vitro to further explore molecular mechanisms action WTAP/YTHDF1 following neural damage. Results The found that m6A levels upregulated at early stage TBI, deletion did not affect function but promoted functional recovery Conditional suppressed neuroinflammation TBI phase: could directly act on mRNA, regulate mRNA level, promote expression neuronal injury. Further investigation YTH domain YTHDF1 bind protein expression. mutation or silencing improved injury, inhibited Caspase-1 activation, decreased IL-1β levels. This effect was mediated via suppression translation, which also reversed stimulative overexpression inflammation. Conclusions Our results indicate participates damage by translation m6A-YTHDF1-dependent manner WTAP/m6A/YTHDF1 downregulation therapeutics viable promising approach preserving can provide support targeted drug development.

Language: Английский

Citations

12
Identification of significant m6A regulators and immune microenvironment characterization in ischemic stroke DOI Creative Commons
Lili Zhao, Dingli Song, Tao Li

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Feb. 11, 2024

The role of m6A modification in the regulation immune microenvironment (IME) ischemic stroke (IS) is barely known. Thus, we aim to investigate impact on IME IS and its diagnostic value IS. We comprehensively assessed patterns, relationship between these patterns characteristics IME. individual sample were quantified by m6Ascore. performance phenotype-related genes as potential biomarkers was evaluated area under receiver operating characteristic curve. Experimental validation also performed qRT-PCR. Six dysregulated regulators identified a classification model consisting four key (METLL3, RBMX, RBM15B, YTDHF3) could distinguish healthy control samples well. METTL3 YTHDF3 are closely related circulating neutrophil abundance. Two distinct determined which differed immunocyte six (APOBEC3A, PTMA, FCGR3A, LOC440926, LOC649946, FTH1L11), further explored their biological function. Among them, APOBEC3A, FTH1L11 positively associated with APOBEC3A FCGR3A stable m6A-associated both discovery cohorts. This study reveals that plays non-negligible formation diversified complex be

Language: Английский

Citations

3
ALKBH5 protects against stroke by reducing endoplasmic reticulum stress-dependent inflammation injury via the STAT5/PERK/EIF2α/CHOP signaling pathway in an m6A-YTHDF1-dependent manner DOI

Chujuan Liu,

Hui Chen,

Tao Xi

et al.

Experimental Neurology, Journal Year: 2023, Volume and Issue: 372, P. 114629 - 114629

Published: Dec. 4, 2023

Language: Английский

Citations

7
Targeting PTEN in ischemic stroke: From molecular mechanisms to therapeutic potentials DOI
Yufei Zheng,

Huiying Gu,

Yu‐Ming Kong

et al.

Experimental Neurology, Journal Year: 2024, Volume and Issue: 383, P. 115023 - 115023

Published: Oct. 25, 2024

Language: Английский

Citations

2
The Diagnostic Model of Ligusticum Chuanxiong Hort. Against Cerebral Stroke Using Network Pharmacology and Transcriptomics Analyses DOI Creative Commons
Jinfeng Zhang,

Chongyin Cai,

Ying Luo

et al.

Journal of Integrative Neuroscience, Journal Year: 2023, Volume and Issue: 22(6)

Published: Oct. 23, 2023

Background: Cerebral stroke is a leading cause of death and disability worldwide. Ligusticum Chuanxiong Hort. (LCH), well-known Chinese herb, widely used for the treatment cerebral stroke. This study aimed to investigate underlying mechanisms LCH in develop diagnostic model. Methods: We employed network pharmacology analyses identify active compounds, targets, treating Molecular docking was performed visualize binding site between core compounds hub targets. Furthermore, model constructed based on transcriptomic analysis. Results: Our findings revealed that contains multiple ingredients, including oleic acid caffeic acid. Protein-protein interaction analysis identified IL1B, CCL2, MAPK3, PTGS2, JUN, MMP9, TLR4, HIF1A, PPARA, FOS, PTEN, NFE2L2, TLR2, TIMP1, SOD2 as top 15 genes. Kyoto Encyclopedia Genes Genomes pathway highlighted enrichment TNF IL-17 signaling pathways. demonstrated sites acid, PPARP, TIMP1. The indicated TLR2 serve blood biomarkers Conclusions: demonstrates alleviates symptoms following through interactions with contribute better understanding therapeutic offer insights into development

Language: Английский

Citations

4
Usf2 Deficiency Promotes Autophagy to Alleviate Cerebral Ischemia-Reperfusion Injury Through Suppressing YTHDF1-m6A-Mediated Cdc25A Translation DOI
Chao Liu, Qing Gao, Jian Dong

et al.

Molecular Neurobiology, Journal Year: 2023, Volume and Issue: 61(5), P. 2556 - 2568

Published: Nov. 2, 2023

Language: Английский

Citations

4
N-methyladenosine modification in ischemic stroke: Functions, regulation, and therapeutic potential DOI Creative Commons
Fei Han

Heliyon, Journal Year: 2024, Volume and Issue: 10(3), P. e25192 - e25192

Published: Jan. 23, 2024

N6-methyladenosine (m6A) modification is the most frequently occurring internal in eukaryotic RNAs. By modulating various aspects of RNA life cycle, it has been implicated a wide range pathological and physiological processes associated with human diseases. Ischemic stroke major cause death disability worldwide few treatment options narrow therapeutic window, accumulating evidence indicated involvement m6A modifications development progression this type stroke. In review, which provides insights for prevention clinical stroke, we present an overview roles played by ischemic from three main perspectives: (1) association established risk factors including hypertension, diabetes mellitus, hyperlipidemia, obesity, heart disease; (2) regulators their functional regulation pathophysiological injury mechanisms namely oxidative stress, mitochondrial dysfunction, endothelial neuroinflammation, cell processes; (3) diagnostic potential

Language: Английский

Citations

1
Loss of Epitranscriptomic Modification N6-Methyladenosine (m6A) Reader YTHDF1 Exacerbates Ischemic Brain Injury in a Sexually Dimorphic Manner DOI
Anil K. Chokkalla, Vijay Arruri,

Suresh L. Mehta

et al.

Translational Stroke Research, Journal Year: 2024, Volume and Issue: unknown

Published: June 13, 2024

Language: Английский

Citations

1
FABP3 Induces Mitochondrial Autophagy to Promote Neuronal Cell Apoptosis in Brain Ischemia-Reperfusion Injury DOI
Fangfang Zhong, Bo Wei,

Guo-Xiang Bao

et al.

Neurotoxicity Research, Journal Year: 2024, Volume and Issue: 42(4)

Published: July 15, 2024

Language: Английский

Citations

1