The good, the bad, and the unknown nature of decreased GD3 synthase expression DOI Creative Commons
Borna Puljko,

Josip Grbavac,

Vinka Potočki

et al.

Frontiers in Molecular Neuroscience, Journal Year: 2024, Volume and Issue: 17

Published: Nov. 22, 2024

This paper explores the physiological consequences of decreased expression GD3 synthase (GD3S), a biosynthetic enzyme that catalyzes synthesis b-series gangliosides. GD3S is key factor in tumorigenesis, with overexpression enhancing tumor growth, proliferation, and metastasis various cancers. Hence, inhibiting activity has potential therapeutic effects due to its role malignancy-associated pathways across different cancer types. also been investigated as promising target treatment neurodegenerative disorders. Drugs targeting have extensively explored underwent clinical trials, however mouse models, human subjects, vitro studies demonstrated serious adverse effects. We highlight these negative show original mass spectrometry imaging (MSI) data indicating inactivated can generally negatively affect energy metabolism, regulatory pathways, mitigation oxidative stress. The disturbance several systems induced by inhibition underscores vital this maintaining cellular homeostasis should be taken into account when considered target.

Language: Английский

The Human Ganglioside Interactome in Live Cells Revealed Using Clickable Photoaffinity Ganglioside Probes DOI

Gao‐Lan Zhang,

Mitchell J. Porter,

Abduselam K. Awol

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(26), P. 17801 - 17816

Published: June 18, 2024

Gangliosides, sialic acid bearing glycosphingolipids, are components of the outer leaflet plasma membranes all vertebrate cells. They contribute to cell regulation by interacting with proteins in their own (cis) or extracellular milieu (trans). As amphipathic membrane constituents, gangliosides present challenges for identifying ganglioside protein interactome. To meet these challenges, we synthesized bifunctional clickable photoaffinity gangliosides, delivered them cultured cells, then captured and identified interactomes using proteomic mass spectrometry. Installing probes on lipid glycan moieties, cis trans ganglioside–protein interactions. Ganglioside varied structure, type, site probe (lipid glycan). Gene ontology revealed that engage transmembrane transporters adhesion including integrins, cadherins, laminins. The approach developed is applicable other types, promising provide insights into molecular cellular gangliosides.

Language: Английский

Citations

8
Rafting on the Evidence for Lipid Raft-like Domains as Hubs Triggering Environmental Toxicants’ Cellular Effects DOI Creative Commons

Dorinda Marques‐da‐Silva,

Ricardo Lagoa

Molecules, Journal Year: 2023, Volume and Issue: 28(18), P. 6598 - 6598

Published: Sept. 13, 2023

The plasma membrane lipid rafts are cholesterol- and sphingolipid-enriched domains that allow regularly distributed, sub-micro-sized structures englobing proteins to compartmentalize cellular processes. These can be highly heterogeneous dynamic, functioning as signal transduction platforms amplify the local concentrations signaling of individual components. Moreover, they participate in cell routes known important targets environmental toxicants affecting redox status calcium homeostasis, immune regulation, hormonal functions. In this work, evidence raft-like operate hubs for toxicants' actions is discussed, suggestions future research provided. Several studies address insertion pesticides other organic pollutants into membranes, their accumulation rafts, or rafts' disruption by polychlorinated biphenyls (PCBs), benzo[a]pyrene (B[a]P), even metals/metalloids. hepatocytes, macrophages, neurons, B[a]P, airborne particulate matter, caused protein remodeling, oxidative changes, amyloidogenesis. Different investigated role invaginated present endothelial cells mediating vascular inflammatory effects PCBs. Furthermore, vitro vivo data strongly implicate raft-localized NADPH oxidases, aryl hydrocarbon receptor, caveolin-1, kinases toxic mechanisms occupational chemicals.

Language: Английский

Citations

16
Glycosphingolipids in congenital disorders of glycosylation (CDG) DOI

Andrea Jáñez Pedrayes,

Daisy Rymen, Bart Ghesquière

et al.

Molecular Genetics and Metabolism, Journal Year: 2024, Volume and Issue: 142(1), P. 108434 - 108434

Published: March 5, 2024

Language: Английский

Citations

3
Gangliosides and Cholesterol: Dual Regulators of Neuronal Membrane Framework in Autism Spectrum Disorder DOI Open Access
Borna Puljko,

Marija Štracak,

Svjetlana Kalanj Bognar

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1322 - 1322

Published: Feb. 4, 2025

Autism spectrum disorder (ASD) is a neurodevelopmental with heterogeneous clinical presentation. Diagnosing ASD complex, and the criteria for diagnosis, as well term ASD, have changed during last decades. Diagnosis made based on observation accomplishment of specific diagnostic criteria, while particular biomarker does not yet exist. However, studies universally report disequilibrium in membrane lipid content, pointing to unique neurolipid signature ASD. This review sheds light possible role cholesterol gangliosides, complex glycosphingolipids, development In addition maintaining integrity, neuronal signaling, synaptic plasticity, these lipids play neurotransmitter release calcium signaling. Evidence linking lipidome changes includes low levels, unusual ganglioside metabolic profiles. symptoms may be mitigated therapeutic interventions targeting composition membranes. restoring equilibrium central nervous system remains challenge. underscores need comprehensive research into metabolism uncover practical insights etiology treatment lipidomics emerges major area research.

Language: Английский

Citations

0
Na+/K+-ATPase: a multifunctional target in type 2 diabetes and pancreatic islets DOI Creative Commons
Lisha Mou, Zhenkun Fu,

Tony Bowei Wang

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 19, 2025

Type 2 diabetes (T2D) is a widespread metabolic disorder marked by hyperglycemia, arising from insulin resistance and relative deficiency. This review investigates the critical role of Na+/K+-ATPase (NKA), transmembrane protein essential for maintaining cellular ion gradients, in pathophysiology T2D. We provide an overview NKA's biological functions, emphasizing its involvement signaling pathways, secretion, glucose homeostasis. The potential NKA as therapeutic target T2D analyzed, showcasing innovative strategies such activators, gene therapy, stem cell therapy aimed at enhancing activity to achieve better glycemic control. Additionally, multifunctional viability modulating immune responses islet transplantation may offer benefits improving transplant outcomes. By elucidating complex interactions between T2D, this aims shed light on developing novel interventions that meet multifaceted needs individuals suffering chronic condition, ultimately their health

Language: Английский

Citations

0
The good, the bad, and the unknown nature of decreased GD3 synthase expression DOI Creative Commons
Borna Puljko,

Josip Grbavac,

Vinka Potočki

et al.

Frontiers in Molecular Neuroscience, Journal Year: 2024, Volume and Issue: 17

Published: Nov. 22, 2024

This paper explores the physiological consequences of decreased expression GD3 synthase (GD3S), a biosynthetic enzyme that catalyzes synthesis b-series gangliosides. GD3S is key factor in tumorigenesis, with overexpression enhancing tumor growth, proliferation, and metastasis various cancers. Hence, inhibiting activity has potential therapeutic effects due to its role malignancy-associated pathways across different cancer types. also been investigated as promising target treatment neurodegenerative disorders. Drugs targeting have extensively explored underwent clinical trials, however mouse models, human subjects, vitro studies demonstrated serious adverse effects. We highlight these negative show original mass spectrometry imaging (MSI) data indicating inactivated can generally negatively affect energy metabolism, regulatory pathways, mitigation oxidative stress. The disturbance several systems induced by inhibition underscores vital this maintaining cellular homeostasis should be taken into account when considered target.

Language: Английский

Citations

0