Sex-specific DNA methylation signatures of autism spectrum disorder from whole genome bisulfite sequencing of newborn blood DOI Creative Commons
Julia S. Mouat, Nickilou Y. Krigbaum, Sophia Hakam

et al.

Biology of Sex Differences, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 30, 2025

Autism spectrum disorder (ASD) is a group of neurodevelopmental conditions currently diagnosed through behavioral assessments in childhood, though neuropathological changes begin utero. ASD more commonly males, disparity attributed to both biological sex differences and diagnostic biases. Identifying molecular biomarkers, such as DNA methylation signatures, could provide objective screening for ASD-risk newborns, allowing early intervention. Epigenetic dysregulation has been reported multiple tissues from newborns who are later with ASD, but this the first study investigate sex-specific signatures newborn blood, an accessible widely banked tissue. We assayed blood typically developing (TD) individuals (discovery set n = 196, replication 90) using whole genome bisulfite sequencing (WGBS). Sex-stratified differentially methylated regions (DMRs) were assessed replication, comparisons by sex, overlaps DMRs other tissues, enrichment processes SFARI genes. found that sexes significantly replicated independent cohort enriched hypomethylation compared TD samples, well location promoters, CpG islands, island shores. By comparing female male we most sex-associated also individuals, alongside additional ASD-specific differences. Female-specific X chromosomal location. Across sexes, overlapped umbilical cord placenta not post-mortem cerebral cortex. all (females) known genes (both sexes). Overall, identified signature supported protective effect highlighted convergence epigenetic genetic newborns. Despite study's limitations, particularly sample sizes, our results demonstrate potential emphasize importance sex-stratification future studies.

Language: Английский

Structural insights into polyisoprenyl-binding glycosyltransferases DOI

Allen P. Zinkle,

Ryan T. Morgan,

Rie Nygaard

et al.

Structure, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

2
On a sugar high: Role of O-GlcNAcylation in cancer DOI Creative Commons

Giang Lê Minh,

Emily M. Esquea,

Riley G. Young

et al.

Journal of Biological Chemistry, Journal Year: 2023, Volume and Issue: 299(11), P. 105344 - 105344

Published: Oct. 12, 2023

Recent advances in the understanding of molecular mechanisms underlying cancer progression have led to development novel therapeutic targeting strategies. Aberrant glycosylation patterns and their implication gained increasing attention as potential targets due critical role regulating tumor-specific pathways that contribute cell survival, proliferation, progression. A special type has been gaining momentum research is modification nuclear, cytoplasmic, mitochondrial proteins, termed O-GlcNAcylation. This protein catalyzed by an enzyme called O-GlcNAc transferase (OGT), which uses final product Hexosamine Biosynthetic Pathway (HBP) connect altered nutrient availability changes cellular signaling multiple aspects tumor Both its OGT are highly elevated fulfill crucial many hallmarks cancer. In this review, we present discuss latest findings elucidating involvement

Language: Английский

Citations

35
Roles of protein post-translational modifications in glucose and lipid metabolism: mechanisms and perspectives DOI Creative Commons
Yuhang Yang, Ri Wen, Ni Yang

et al.

Molecular Medicine, Journal Year: 2023, Volume and Issue: 29(1)

Published: July 6, 2023

Abstract The metabolism of glucose and lipids is essential for energy production in the body, dysregulation metabolic pathways these molecules implicated various acute chronic diseases, such as type 2 diabetes, Alzheimer’s disease, atherosclerosis (AS), obesity, tumor, sepsis. Post-translational modifications (PTMs) proteins, which involve addition or removal covalent functional groups, play a crucial role regulating protein structure, localization function, activity. Common PTMs include phosphorylation, acetylation, ubiquitination, methylation, glycosylation. Emerging evidence indicates that are significant modulating lipid by modifying key enzymes proteins. In this review, we summarize current understanding regulatory mechanisms metabolism, with focus on their involvement disease progression associated aberrant metabolism. Furthermore, discuss future prospects PTMs, highlighting potential gaining deeper insights into related diseases.

Language: Английский

Citations

33
Role of Tau Protein in Neurodegenerative Diseases and Development of Its Targeted Drugs: A Literature Review DOI Creative Commons
J Yang,

Weijia Zhi,

Lifeng Wang

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(12), P. 2812 - 2812

Published: June 13, 2024

Tau protein is a microtubule-associated that widely distributed in the central nervous system and maintains regulates neuronal morphology function. aggregates abnormally forms neurofibrillary tangles neurodegenerative diseases, disrupting structure function of neurons leading to death, which triggers initiation progression neurological disorders. The aggregation tau diseases associated with post-translational modifications, may affect hydrophilicity, spatial conformation, stability protein, promoting formation tangles. Therefore, studying role mechanism aberrant important for understanding finding therapeutic approaches. This review describes possible mechanisms by promotes modifications influencing factors, current status drug discovery development related contribute new approaches alleviate or treat diseases.

Language: Английский

Citations

15
Precise Structural Analysis of Neutral Glycans Using Aerolysin Mutant T240R Nanopore DOI
Wenqi Lu, Xinjia Zhao, Minmin Li

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: 18(19), P. 12412 - 12426

Published: May 2, 2024

Glycans play vital roles in nearly all life processes of multicellular organisms, and understanding these activities is inseparable from elucidating the biological significance glycans. However, glycan research has lagged behind that DNA protein due to challenges posed by structural heterogeneity isomerism (i.e., structures with equal molecular weights) lack high-efficiency analysis techniques. Nanopore technology emerged as a sensitive single-molecule biosensor, shining light on analysis. significant number glycans are small uncharged, making it challenging elicit identifiable nanopore signals. Here we introduce

Language: Английский

Citations

10
Glycosylation Pathways Targeted by Deregulated miRNAs in Autism Spectrum Disorder DOI Open Access
Federica Mirabella, Martina Randazzo,

Alessandro Rinaldi

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 783 - 783

Published: Jan. 17, 2025

Autism Spectrum Disorder (ASD) is a complex condition with multifactorial aetiology including both genetic and epigenetic factors. MicroRNAs (miRNAs) play role in ASD may influence metabolic pathways. Glycosylation (the glycoconjugate synthesis pathway) necessary process for the optimal development of central nervous system (CNS). Congenital Disorders (CDGs) are linked to over 180 genes predominantly associated neurodevelopmental disorders (NDDs) ASD. From literature search, we considered 64 miRNAs consistently deregulated patients (ASD-miRNAs). Computational tools, DIANA-miRPath v3.0 TarBase v8, were employed investigate potential involvement ASD-miRNAs glycosylation A regulatory network constructed through miRNet 2.0 revealed these targeting glycosylation. Protein functions further validated Human Atlas. total twenty-five identified, nine that differentially expressed cells or brain tissue pathways, specifically protein N- O-glycosylation glycosaminoglycan biosynthesis (heparan sulfate). number CDG and/or ASD-risk genes, DOLK, GALNT2, EXT1, identified as targets, along interactions involving four key (hsa-miR-423-5p, hsa-miR-30c-5p, hsa-miR-195-5p, hsa-miR-132-5p). B4GALT1, an susceptibility gene, emerged hub, reinforcing link between In sum, evidence presented here supports hypothesis mediate regulation glycosylation, thus unveiling possible novel patho-mechanisms underlying

Language: Английский

Citations

1
A Closer Look at Dystonia with the Glycosylation DOI Creative Commons

Hours Camille,

Pierre Gressèns

Cellular and Molecular Neurobiology, Journal Year: 2025, Volume and Issue: 45(1)

Published: March 18, 2025

Graphical Abstract

Language: Английский

Citations

1
N-Glycosylation as a Modulator of Protein Conformation and Assembly in Disease DOI Creative Commons
Chiranjeevi Pasala, Sahil Sharma, Tanaya Roychowdhury

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(3), P. 282 - 282

Published: Feb. 27, 2024

Glycosylation, a prevalent post-translational modification, plays pivotal role in regulating intricate cellular processes by covalently attaching glycans to macromolecules. Dysregulated glycosylation is linked spectrum of diseases, encompassing cancer, neurodegenerative disorders, congenital infections, and inflammation. This review delves into the interplay between protein conformation, with specific focus on profound impact N-glycans selection distinct conformations characterized interactomes—namely, assemblies—under normal pathological conditions across various diseases. We begin examining spike SARS virus, illustrating how regulate infectivity pathogenic agents. Subsequently, we utilize prion chaperone glucose-regulated 94 as examples, exploring instances where N-glycosylation transforms physiological structures disease-associated forms. Unraveling these connections provides valuable insights potential therapeutic avenues deeper comprehension molecular intricacies that underlie disease conditions. exploration glycosylation’s influence conformation effectively bridges gap glycome disease, offering comprehensive perspective implications targeting conformational mutants their pathologic assemblies The goal unravel nuances modifications, shedding light they contribute assembly, disease.

Language: Английский

Citations

8
Early-life perfluorooctanoic acid exposure disrupts the function of dopamine transporter protein with glycosylation changes implicating the links between decreased dopamine levels and disruptive behaviors in larval zebrafish DOI
Yatao Du, Qin Li, Guangdi Zhou

et al.

The Science of The Total Environment, Journal Year: 2024, Volume and Issue: 917, P. 170408 - 170408

Published: Jan. 26, 2024

Language: Английский

Citations

5
Mass Spectrometric Analysis of Urinary N-Glycosylation Changes in Patients with Parkinson’s Disease DOI
Mingming Xu,

Hong Jin,

Wei Ge

et al.

ACS Chemical Neuroscience, Journal Year: 2023, Volume and Issue: 14(18), P. 3507 - 3517

Published: Sept. 7, 2023

Urine is thought to provide earlier and more sensitive molecular changes for biomarker discovery than blood. Numerous glycoproteins, peptides, free glycans are present in urine through glomerular filtration of plasma, cell shedding, apoptosis, proteolytic cleavage, exosome secretion. biomarkers have enormous diagnostic potential, the use these a long-standing practice. The non-urological disease from also gaining attention due its non-invasive sample collection ease analysis. Abnormal protein glycosylation plasma or cerebrospinal fluid has been associated with Parkinson's disease, however, whether characteristic remains be explored. Here, we mass spectrometry-based glycomics glycoproteomics approaches analyze samples glycans, glycosites, intact glycopeptides samples. Reduced abundance N-glycans was detected at level total as well specific glycosites glycopeptides. most abundant N-glycan S(6)1H5N4F1; S(6)2H5N4 N4H4F1 highly serum urine, 10 biantennary galactosylated PD patients were significantly decreased. downregulation sialylation may reduction ST3GAL2. Site-specific N-glycosylation analysis revealed that AMBP, UMOD, RNase1 PD-specific sites. GO KEGG clues identify disease-specific disease.

Language: Английский

Citations

12