Exploring potential key genes and disease mechanisms in Εarly-onset genetic epilepsy via integrated bioinformatics analysis DOI Creative Commons

Vasiliki Boulaki,

Spiros Efthimiopoulos, Nicholas Κ. Moschonas

и другие.

Neurobiology of Disease, Год журнала: 2025, Номер unknown, С. 106888 - 106888

Опубликована: Апрель 1, 2025

Epilepsy is a severe common neurological disease affecting all ages. with onset before the age of 5 years, designated early-onset epilepsy (EOE), special importance. According to previous studies, genetic factors contribute significantly pathogenesis EOE that remains unclear and must be explored. So, list 229 well-selected EOE-associated genes expressed in brain was created for investigation molecular mechanisms involved its pathogenesis. Enrichment analysis showed among significant pathways were nicotine addiction, GABAergic synapse, synaptic vesicle cycle, regulation membrane potential, cholinergic dopaminergic morphine addiction. Performing an integrated as well protein-protein interaction network-based approaches use GO, KEGG, ClueGO, cytoHubba 3 network metrics, 12 hub identified, seven which, CDKL5, GABRA1, KCNQ2, KCNQ3, SCN1A, SCN8A STXBP1, identified key (via Venn diagram analysis). These are mostly enriched SNARE interactions vesicular transport, potential exocytosis. Clustering PPI via MCODE functional modules, indicating also other such N-Glycan biosynthesis protein N-linked glycosylation, retrograde endocannabinoid signaling, mTOR signaling aminoacyl-tRNA biosynthesis. Drug-gene number drugs medications EOE, which non-FDA approved azetukalner (under clinical development), indiplon ICA-105665 FDA retigabine, ganaxolone methohexital.

Язык: Английский

Mesoporous materials for glycopeptide separation DOI

Yiting Luo,

Baichun Wang,

Linhua Yi

и другие.

TrAC Trends in Analytical Chemistry, Год журнала: 2023, Номер 167, С. 117234 - 117234

Опубликована: Авг. 16, 2023

Язык: Английский

Процитировано

14
Hypomorphic variants of SEL1L-HRD1 ER-associated degradation are associated with neurodevelopmental disorders DOI Creative Commons
Huilun Wang, Liangguang Leo Lin,

Zexin Jason Li

и другие.

Journal of Clinical Investigation, Год журнала: 2023, Номер 134(2)

Опубликована: Ноя. 9, 2023

Recent studies using cell type-specific knockout mouse models have improved our understanding of the pathophysiological relevance suppressor lin-12-like-HMG-CoA reductase degradation 1 (SEL1L-HRD1) endoplasmic reticulum-associated (ER-associated) (ERAD); however, its importance in humans remains unclear, as no disease variant has been identified. Here, we report identification 3 biallelic missense variants SEL1L and HRD1 (or SYVN1) 6 children from independent families presenting with developmental delay, intellectual disability, microcephaly, facial dysmorphisms, hypotonia, and/or ataxia. These (p.Gly585Asp, p.Met528Arg) (p.Pro398Leu) were hypomorphic impaired ERAD function at distinct steps ERAD, including substrate recruitment (SEL1L p.Gly585Asp), SEL1L-HRD1 complex formation p.Met528Arg), activity (HRD1 p.Pro398Leu). Our study not only provides insights into structure-function relationship but also establishes humans.

Язык: Английский

Процитировано

14
Interferon-Inducible Guanylate-Binding Protein 5 Inhibits Replication of Multiple Viruses by Binding to the Oligosaccharyltransferase Complex and Inhibiting Glycoprotein Maturation DOI Creative Commons
Shaobo Wang, Wanyu Li, Lingling Wang

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Май 3, 2024

Abstract Viral infection induces production of type I interferons and expression interferon-stimulated genes (ISGs) that play key roles in inhibiting viral infection. Here, we show the ISG guanylate-binding protein 5 (GBP5) inhibits N-linked glycosylation proteins multiple viruses, including SARS-CoV-2 spike protein. GBP5 binds to accessory subunits host oligosaccharyltransferase (OST) complex blocks its interaction with protein, which results misfolding retention endoplasmic reticulum likely due decreased N -glycan transfer, reduces assembly release infectious virions. Consistent these observations, pharmacological inhibition OST NGI-1 potently other proteins, MERS-CoV HIV-1 gp160, IAV hemagglutinin, prevents Our identify a novel strategy by ISGs restrict virus provide rationale for targeting as broad antiviral therapeutic strategy. Highlights The gene is induced vitro vivo. ER-localized restricts leading preventing transport Golgi apparatus. potentially access catalytic subunit N-glycosylation Pharmacological cell SARS-CoV-2, variants concern, HIV-1, IAV. Significance We found SARS-CoV-2. Importantly, Oligosaccharyltransferase Complex IAV, indicating future translational application our findings.

Язык: Английский

Процитировано

6
Lactylome analysis reveals potential target modified proteins in the retina of form-deprivation myopia DOI Creative Commons
Jiaojiao Feng, Xiaoniao Chen, Runkuan Li

и другие.

iScience, Год журнала: 2024, Номер 27(9), С. 110606 - 110606

Опубликована: Июль 29, 2024

The biological mechanisms underlying the development of myopia have not yet been completely elucidated. retina is critical for visual signal processing, which primarily utilizes aerobic glycolysis to produce lactate as a metabolic end product. Lactate facilitates lysine lactylation (Kla), posttranslational modification essential transcriptional regulation. This study found increased glycolytic flux and accumulation in retinas form-deprived myopic guinea pigs. Subsequently, comprehensive analysis Kla levels retinal proteins revealed that was upregulated at 124 sites 92 downregulated three proteins. Functional enrichment protein interaction analyses showed significant pathways related energy metabolism, including glutathione glycolysis, hypoxia-inducible factor-1 signaling pathway. Parallel-reaction monitoring confirmed data reliability. These findings suggest connection between metabolism imbalance, providing new insights into pathogenesis myopia.

Язык: Английский

Процитировано

5
In situ microwave fixation provides an instantaneous snapshot of the brain metabolome DOI Creative Commons
Jelena A. Juras, Madison B. Webb, Lyndsay E.A. Young

и другие.

Cell Reports Methods, Год журнала: 2023, Номер 3(4), С. 100455 - 100455

Опубликована: Апрель 1, 2023

Brain glucose metabolism is highly heterogeneous among brain regions and continues postmortem. In particular, we demonstrate exhaustion of glycogen an increase in lactate production during conventional rapid resection preservation by liquid nitrogen. contrast, show that these postmortem changes are not observed with simultaneous animal sacrifice situ fixation focused, high-power microwave. We further employ microwave to define the mouse model streptozotocin-induced type 1 diabetes. Using both total pool isotope tracing analyses, identified global hypometabolism multiple regions, evidenced reduced 13C enrichment into glycogen, glycolysis, tricarboxylic acid (TCA) cycle. Reduced correlated a marked decrease GLUT2 expression several metabolic enzymes unique regions. conclusion, our study supports incorporation for more accurate studies rodent models.

Язык: Английский

Процитировано

11
Advances in protein glycosylation and its role in tissue repair and regeneration DOI

Zhongyu Yue,

Yajie Yu,

Boyuan Gao

и другие.

Glycoconjugate Journal, Год журнала: 2023, Номер 40(3), С. 355 - 373

Опубликована: Апрель 25, 2023

Язык: Английский

Процитировано

11
Human-specific features and developmental dynamics of the brain N-glycome DOI Creative Commons
Thomas Klarić, Ivan Gudelj, Gabriel Santpere

и другие.

Science Advances, Год журнала: 2023, Номер 9(49)

Опубликована: Дек. 6, 2023

Comparative "omics" studies have revealed unique aspects of human neurobiology, yet an evolutionary perspective the brain N-glycome is lacking. We performed multiregional characterization rat, macaque, chimpanzee, and N-glycomes using chromatography mass spectrometry then integrated these data with complementary glycotranscriptomic data. found that, in primates, has diverged more rapidly than underlying transcriptomic framework, providing a means for generating additional interspecies diversity. Our suggest that evolution hominids been characterized by overall increase complexity coupled shift toward increased usage α(2-6)-linked N-acetylneuraminic acid. Moreover, differences cell type expression pattern key glycogenes were identified, including some human-specific differences, which may underpin this divergence. Last, comparing prenatal adult N-glycomes, we uncovered region-specific neurodevelopmental pathways lead to distinct spatial N-glycosylation profiles mature brain.

Язык: Английский

Процитировано

10
DHEC mesylate attenuates pathologies and aberrant bisecting N-glycosylation in Alzheimer's disease models DOI
Yue Wang,

Yiming Cao,

Hongfei Huang

и другие.

Neuropharmacology, Год журнала: 2024, Номер 248, С. 109863 - 109863

Опубликована: Фев. 6, 2024

Язык: Английский

Процитировано

4
Neurological glycogen storage diseases and emerging therapeutics DOI Creative Commons
Matthieu Colpaert, Pankaj K. Singh,

Katherine J. Donohue

и другие.

Neurotherapeutics, Год журнала: 2024, Номер unknown, С. e00446 - e00446

Опубликована: Сен. 1, 2024

Язык: Английский

Процитировано

4
Sugar-coated bullets: Unveiling the enigmatic mystery ‘sweet arsenal’ in osteoarthritis DOI Creative Commons
Hongzhi Liu,

Xinqiu Song,

Hongmei Zhang

и другие.

Heliyon, Год журнала: 2024, Номер 10(6), С. e27624 - e27624

Опубликована: Март 1, 2024

Glycosylation is a crucial post-translational modification process where sugar molecules (glycans) are covalently linked to proteins, lipids, or other biomolecules. In this highly regulated and complex process, series of enzymes involved in adding, modifying, removing residues. This plays pivotal role various biological functions, influencing the structure, stability, functionality modified molecules. essential numerous processes, including cell adhesion, signal transduction, immune response, biomolecular recognition. Dysregulation glycosylation associated with diseases. Glycation, characterized by non-enzymatic attachment has also emerged as factor review comprehensively explores multifaceted glycation disease pathogenesis, specific focus on its implications osteoarthritis (OA). alterations wield profound influence OA intertwining onset progression. Diverse studies underscore aberrant OA, particularly emphasizing intricate relationship joint tissue degradation inflammatory cascades. Distinct patterns, N-glycans O-glycans, showcase correlations cytokines, matrix metalloproteinases, cellular senescence pathways, amplifying degenerative processes within cartilage. Furthermore, impact advanced end-products (AGEs) formation pathophysiology unveils critical insights into glycosylation-driven chondrocyte behavior extracellular remodeling. These findings illuminate potential therapeutic targets diagnostic markers, signaling promising avenue for targeted interventions management. comprehensive review, we aim thoroughly examine significant AGEs explore varied effects related conditions, such liver-related diseases, system disorders, cancers, among others. By glycosylation's beyond uncover that extend immediate potentially revealing novel perspectives diagnosing treating OA.

Язык: Английский

Процитировано

3