Cholesterol-Dependent Serotonin Insertion Controlled by Gangliosides in Model Lipid Membranes DOI Open Access
Jacques Fantini, Fodil Azzaz,

Ryad Bennaï

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(18), P. 10194 - 10194

Published: Sept. 23, 2024

Serotonin is distinct among synaptic neurotransmitters because it amphipathic and released from vesicles at concentrations superior to its water solubility limit (270 mM in for a of 110 mM). Hence, serotonin mostly aggregated the cleft, due extensive aromatic stacking. This important characteristic has received scant attention, as most representations serotonergic synapse take warranted that molecules are present monomers after vesicle exocytosis. Using combination silico physicochemical approaches new experimental device mimicking conditions, we show aggregates efficiently dissolved by gangliosides (especially GM1) postsynaptic membranes. initial interaction, driven electrostatic forces, attracts insoluble resolves micelles into monomers. also interacts with cholesterol via set CH-π van der Waals interactions. Thus, act together functional serotonin-collecting funnel on brain cell Based this unique mode interaction membranes, propose model transmission takes account post-exocytosis solubilizing effect aggregates.

Language: Английский

Conformationally adaptive therapeutic peptides for diseases caused by intrinsically disordered proteins (IDPs). New paradigm for drug discovery: Target the target, not the arrow DOI Creative Commons
Jacques Fantini, Fodil Azzaz, Coralie Di Scala

et al.

Pharmacology & Therapeutics, Journal Year: 2025, Volume and Issue: unknown, P. 108797 - 108797

Published: Jan. 1, 2025

The traditional model of protein structure determined by the amino acid sequence is today seriously challenged fact that approximately half human proteome made up proteins do not have a stable 3D structure, either partially or in totality. These proteins, called intrinsically disordered (IDPs), are involved numerous physiological functions and associated with severe pathologies, e.g. Alzheimer, Parkinson, Creutzfeldt-Jakob, amyotrophic lateral sclerosis (ALS), type 2 diabetes. Targeting these challenging for two reasons: i) we need to preserve their functions, ii) drug design molecular docking possible due lack reliable starting conditions. Faced this challenge, solutions proposed artificial intelligence (AI) such as AlphaFold clearly unsuitable. Instead, suggest an innovative approach consisting mimicking, short synthetic peptides, conformational flexibility IDPs. which call adaptive derived from domains IDPs become structured after interacting ligand. Adaptive peptides designed aim selectively antagonizing harmful effects IDPs, without targeting them directly but through selected ligands, affecting properties. This"target target, arrow" strategy promised open new route discovery currently undruggable proteins.

Language: Английский

Citations

2
Glutamate, Gangliosides, and the Synapse: Electrostatics at Work in the Brain DOI Open Access
Henri Chahinian, Nouara Yahi, Jacques Fantini

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(16), P. 8583 - 8583

Published: Aug. 6, 2024

The synapse is a piece of information transfer machinery replacing the electrical conduction nerve impulses at end neuron. Like many biological mechanisms, its functioning heavily affected by time constraints. solution selected evolution based on chemical communication that, in theory, cannot compete with speed conduction. Nevertheless, biochemical and biophysical compensation mechanisms mitigate this intrinsic weakness: (i) through high concentrations neurotransmitters inside synaptic vesicles; (ii) concentration neurotransmitter receptors lipid rafts, which are signaling platforms; indeed, presence raft lipids, such as gangliosides cholesterol, allows fine tuning these lipids; (iii) negative charges gangliosides, generate an attractive (for cationic neurotransmitters, serotonin) or repulsive anionic glutamate) electric field. This field controls flow glutamate tripartite involving pre- post-synaptic neurons astrocyte. Changes expression brain can disrupt glutamatergic synapse, causing fatal diseases, Rett syndrome. In review, we propose in-depth analysis role highlighting primordial generally overlooked played gangliosides.

Language: Английский

Citations

4
ADSORPTION OF ORGANIC COMPOUNDS AND HAZARDOUS MICROORGANISMS FROM SEWAGE AND SURFACTANT-CONTAINING WASTEWATER USING CARBON-BASED NANOMATERIALS: A FOCUS ON GRAPHENE OXIDE AND CARBON NANOTUBE DOI Creative Commons
Ayesha Younas,

M. N. Rashad,

Ayesha Rafaqat

et al.

Biological and Clinical Sciences Research Journal, Journal Year: 2024, Volume and Issue: 2024(1), P. 1052 - 1052

Published: Aug. 24, 2024

This review comprehensively examines the utilization of carbon-based nanomaterials, specifically graphene oxide (GO) and carbon nanotubes (CNTs), in advanced wastewater treatment applications. GO CNTs demonstrate exceptional efficacy adsorbing a broad spectrum organic compounds hazardous microorganisms due to their unique physicochemical properties, such as large specific surface areas, high aspect ratios, versatile chemical modifications enabled by functional groups. is characterised abundant oxygen-containing groups, including hydroxyl, carboxyl, epoxy, which enhance its hydrophilicity adsorption potential for cationic pollutants. Meanwhile, CNTs, available single-walled (SWCNTs) multi-walled (MWCNTs), are noted tubular structure, tensile strength, significant electrical conductivity, making them highly effective molecules heavy metals. The explores mechanisms action these encompass physical through van der Waals forces π-π interactions, well involving covalent or ionic bond formation with contaminants. Recent innovations hybrid systems that integrate other technologies, photocatalysis membrane filtration, highlighted enhancing contaminant removal energy efficiency water purification processes. addresses critical challenges related nanoparticle stability, recovery, production costs, environmental health impacts deploying nanomaterials practical Crucial issues, aggregation, reusability, safe disposal used materials, identified, solutions improve dispersion incorporation magnetic nanoparticles easier recovery. findings emphasise advancing remediation offering promising avenues developing cleaner more efficient solutions. As field progresses, continued exploration interdisciplinary collaboration promise substantial protection advancements.

Language: Английский

Citations

1
Cholesterol-Dependent Serotonin Insertion Controlled by Gangliosides in Model Lipid Membranes DOI Open Access
Jacques Fantini, Fodil Azzaz,

Ryad Bennaï

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(18), P. 10194 - 10194

Published: Sept. 23, 2024

Serotonin is distinct among synaptic neurotransmitters because it amphipathic and released from vesicles at concentrations superior to its water solubility limit (270 mM in for a of 110 mM). Hence, serotonin mostly aggregated the cleft, due extensive aromatic stacking. This important characteristic has received scant attention, as most representations serotonergic synapse take warranted that molecules are present monomers after vesicle exocytosis. Using combination silico physicochemical approaches new experimental device mimicking conditions, we show aggregates efficiently dissolved by gangliosides (especially GM1) postsynaptic membranes. initial interaction, driven electrostatic forces, attracts insoluble resolves micelles into monomers. also interacts with cholesterol via set CH-π van der Waals interactions. Thus, act together functional serotonin-collecting funnel on brain cell Based this unique mode interaction membranes, propose model transmission takes account post-exocytosis solubilizing effect aggregates.

Language: Английский

Citations

1