Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown
Published: Jan. 1, 2024
Language: Английский
Journal of Chemical Information and Modeling, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 14, 2025
N-Methyl-d-aspartate (NMDA) receptors, a subtype of ionotropic glutamate receptors in the central nervous system (CNS), have garnered attention for their role brain disorders. Specifically, GluN2A-containing NMDA emerged as potential therapeutic target treatment depressive disorders and epilepsy. However, development receptor-selective antagonists, represented by N-(4-(2-benzoylhydrazine-1-carbonyl)benzyl)-3-chloro-4-fluorobenzenesulfonamide (TCN-201) its derivatives, faces significant challenge due to limited ability penetrate blood-brain barrier (BBB), hampering vivo characterization further advancement. In this study, we reported series 2-((5-(phemylamino)-1,3,4-thiadiazol-2-yl)thio)-N-(cyclohexylmethyl)acetamide achieved through structure-guided optimization strategy using free energy perturbation (FEP) BBB permeability estimation. Through systematic exploration various phenyl substitutions, compound 1f standout compound, demonstrating substantially enhanced inhibitory activity compared with lead TCN-213. Compound not only displayed satisfactory but also showed antidepressant-like potency hydrocortisone-induced zebrafish depression-like model. All results position it promising candidate developing innovative therapeutics receptor-related
Language: Английский
Citations
1
Biomolecules, Journal Year: 2024, Volume and Issue: 14(5), P. 589 - 589
Published: May 16, 2024
Excitotoxicity is a common pathological process in neurological diseases caused by excess glutamate. The purpose of this study was to evaluate the effect gypenoside XVII (GP-17), monomer, on glutamatergic system. In vitro, rat cortical nerve terminals (synaptosomes), GP-17 dose-dependently decreased glutamate release with an IC50 value 16 μM. removal extracellular Ca2+ or blockade N-and P/Q-type channels and protein kinase A (PKA) abolished inhibitory from synaptosomes. also significantly reduced phosphorylation PKA, SNAP-25, synapsin I vivo model excitotoxicity induced kainic acid (KA), pretreatment prevented seizures rescued neuronal cell injury elevation cortex. expression levels sodium-coupled neutral amino transporter 1, synthesis enzyme glutaminase vesicular 1 but increased level metabolism dehydrogenase cortex KA-treated rats. addition, KA-induced alterations N-methyl-D-aspartate receptor subunits GluN2A GluN2B were pretreatment. decrease cerebral blood flow arginase II expression. These results suggest that (i) GP-17, through suppression N- consequent PKA-mediated SNAP-25 phosphorylation, reduces exocytosis synaptosomes; (ii) has neuroprotective rats regulating synaptic flow.
Language: Английский
Citations
7
Cellular and Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 44(1)
Published: Nov. 23, 2024
Photobiomodulation (PBM) is a safe and effective neurotherapy that modulates cellular pathways by altering cell membrane potentials, leading to beneficial biological effects such as anti-inflammatory neuroregenerative responses. This review compiles studies from PubMed up March 2024, investigating the impact of light at wavelengths ranging 620 1270 nm on ion channels. Out 330 articles screened, 19 met inclusion criteria. Research indicates PBM can directly affect various channels influencing neurotransmitter synthesis in neighboring cells, impacting receptors like glutamate acetylcholine, well potassium, sodium channels, transient receptor potential The diversity hampers comprehensive meta-analysis for evaluating treatment strategies effectively. systematic aims explore role optoelectronic signal transduction PBM, studying neurobiological mechanisms therapeutic significance However, lack uniformity current methods underscores necessity establishing standardized reliable approaches. promising neurotherapeutic approach with through its analyzes studies, revealing influence channel activity emphasizing need protocols.
Language: Английский
Citations
4
International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(19), P. 10668 - 10668
Published: Oct. 3, 2024
Cognitive impairment is a core feature of schizophrenia, playing pivotal role in the pathogenesis and prognosis this disorder. schizophrenia encompasses wide range domains, including processing speed, episodic memory, working executive function. These deficits persist throughout course illness significantly impact functional outcomes quality life. Therefore, it imperative to identify biological basis cognitive develop effective treatments. The N-methyl-D-aspartate (NMDA) receptors synaptic transmission plasticity has long been recognized, making them potential targets for treatment. This review will focus on emerging pharmacology targeting NMDA receptors, offering strategies prevention treatment schizophrenia.
Language: Английский
Citations
4
European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 177690 - 177690
Published: April 1, 2025
Language: Английский
Citations
0
Frontiers in Chemistry, Journal Year: 2024, Volume and Issue: 11
Published: Jan. 19, 2024
Introduction: Epilepsy is a chronic brain disease characterized by repeated seizures and caused excessive glutamate receptor activation. Many plants are traditionally used in the treatment of this disease. This study aimed to evaluate bioavailability polyphenolic extract obtained from Origanum majorana L. (OMP) leaves, as well its antiepileptic activity potential mechanism action. Methods: We have developed validated simple, rapid, accurate stability-indicating reversed-phase liquid chromatographic method for simultaneous determination caffeine quercetin rat plasma. The OMP effect was evaluated with pilocarpine-induced seizures, docking determine possible interaction between caffeic acid N-methyl-D-aspartate (NMDA) receptor. Results Discussion: Both compounds tested showed low unchanged form. However, an anticonvulsant due considerably delayed onset pilocarpine model at dose 100 mg/kg. molecular proved high-affinity NMDA Taken together, OLP polyphenols demonstrated good activity, probably quercetin, acid, or their metabolites
Language: Английский
Citations
3
Neuroscience, Journal Year: 2025, Volume and Issue: 572, P. 108 - 121
Published: March 8, 2025
Language: Английский
Citations
0
medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown
Published: March 27, 2025
Type 2 diabetes (T2DM) is associated with brain abnormalities and cognitive dysfunction, including increased risk for Alzheimer's disease. However, the mechanisms of T2DM-related dementia remain poorly understood. We obtained retrospective data from Mayo Clinic Study Aging 271 individuals T2DM 542 demographically matched non-diabetic controls (age 51-89, 62% male). identified regions significant gray matter atrophy in group then determined which genes were significantly expressed these using imaging transcriptomics. selected 15 candidate involved insulin signaling, lipid metabolism, amyloid processing, N-methyl-D-aspartate-mediated neurotransmission, calcium signaling. The demonstrated default mode, frontal-parietal, sensorimotor networks (p < 0.05 cluster threshold corrected false discovery rate, FDR). IRS1, AKT1, PPARG, PRKAG2 , GRIN2B same (R > 0.10, p 0.03, FDR corrected). Bayesian network analysis indicated directional paths among all 5 as well Clinical Dementia Rating score. Directional altered (Structural Hamming Distance = 12, 0.004), PPARG expression becoming more important context pathophysiology. Alterations transcriptome patterns occurred absence deficit or accumulation, potentially representing an early biomarker dementia.
Language: Английский
Citations
0
Neuropharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 110453 - 110453
Published: April 1, 2025
Language: Английский
Citations
0
Pharmacology & Therapeutics, Journal Year: 2025, Volume and Issue: unknown, P. 108888 - 108888
Published: May 1, 2025
Language: Английский
Citations
0