Search results for "Receptor"

Artemisinin–Second Career as Anticancer Drug?

2015

Artemisinin represents a showcase example not only for the activity of medicinal herbs deriving from traditional chinese medicine, but for phytotherapy in general. Its isolation from Sweet Wormwood (qinhao, Artemisia annua L.) represents the starting point for an unprecedent success story in the treatment of malaria worldwide. Beyond the therapeutic value against Plasmodium parasites, it turned out in recent years that the bioactivity of artemisinin is not restricted to malaria. We and others found that this sesquiterpenoid also exerts profound anticancer activity in vitro and in vivo. Artemisinin-type drugs exert multi-factorial cellular and molecular actions in cancer cells. Ferrous iron …

PGK1-AR axis: Benefits of a novel actor in PCOS pathology.

2020

IN THE SEARCH OF LEPTIN AGONISTS AS ANTI-OBESITY DRUGS: PROTEIN/PROTEIN DOCKING, MOLECULAR DYNAMICS, AND VIRTUAL SCREENING

2012

The body weight control is a mechanism thinly regulated by several hormonal, metabolic, and nervous pathways (1). Recessive homozygous mutations in the ob/ob and db/db mouse strain cause extreme obesity. The products of the ob and db genes are leptin and its receptor, respectively. The leptin receptor is crucial for energy homeostasis and regulation of food uptake. Leptin is a 16 kDa hormone that is mainly secreted by fat cells into the bloodstream. Under normal circumstances, circulating leptin levels are proportionate to the fat body mass. Sensing of elevated leptin levels by the hypothalamic neurocircutry activates a negative feedback loop resulting in reduced food intake and increased e…

Blue-copper binding proteins of Medicago truncatula: Characterization of the expression of two genes related to the arbuscular mycorrhizal symbiosis

2009

International audience; Expression profiling of two paralogous arbuscular mycorrhizal (AM)-specific blue copper-binding gene (MtBcpla and MtBcp1b) isoforms was performed by real-time quantitative polymerase chain reaction in wild-type Medicago truncatula Jemalong 5 (J5) during the mycorrhizal development with Glomus intraradices for up to 7 weeks. Timecourse analysis in J5 showed that expression of both MtBcp1 genes increased continuously and correlated strongly with the colonization intensity and arbuscule content. MtPT4, selected as a reference gene of the functional plant-fungus association, showed a weaker correlation to mycorrhizal development. In a second experiment, a range of mycorr…

A novel putative interactor for the low density lipoprotein receptor cytoplasmic domain

2011

Familial hypercholesterolemia (FH) is a genetic disease mainly caused by mutations in the low density lipoprotein receptor (LDLLDLLDL-R) gene. However, FH-like phenotypes may also arise from mutations occurring in other genes, the products of which normally interact with the LDLLDLLDL receptor. Although several FH-associated proteins have been discovered, many FH-like phenotypes cannot be linked to mutations in already characterized genes, suggesting the existence of other genes still to be identified, the mutations of which may be directly linked to the FH disorder. In order to identify new putative LDLLDLLDLr interactors possibly involved in its internalization and/or sorting, the cytopla…

Discovery of Retinoic Acid-Related Orphan Receptor γt Inverse Agonists via Docking and Negative Image-Based Screening

2018

Retinoic acid-related orphan receptor γt (RORγt) has a vital role in the differentiation of T-helper 17 (TH17) cells. Potent and specific RORγt inverse agonists are sought for treating TH17-related diseases such as psoriasis, rheumatoid arthritis, and type 1 diabetes. Here, the aim was to discover novel RORγt ligands using both standard molecular docking and negative image-based screening. Interestingly, both of these in silico techniques put forward mostly the same compounds for experimental testing. In total, 11 of the 34 molecules purchased for testing were verified as RORγt inverse agonists, thus making the effective hit rate 32%. The pIC50 values for the compounds varied from 4.9 (11 μ…

Chiral hemicucurbit[8]uril as an anion receptor: selectivity to size, shape and charge distribution

2017

A novel eight-membered macrocycle of the hemicucurbit[n]uril family, chiral (all-R)-cyclohexanohemicucurbit[8]uril (cycHC[8]) binds anions in a purely protic solvent with remarkable selectivity. The cycHC[8] portals open and close to fully encapsulate anions in a 1 : 1 ratio, resembling a molecular Pac-Man™. Comprehensive gas, solution and solid phase studies prove that the binding is governed by the size, shape and charge distribution of the bound anion. Gas phase studies show an order of SbF6− ≈ PF6− > ReO4− > ClO4− > SCN− > BF4− > HSO4− > CF3SO3− for anion complexation strength. An extensive crystallographic study reveals the preferred orientations of the anions within the octahedral cav…

The Life Cycle of the Mu-Opioid Receptor

2020

Opioid receptors (ORs) are undisputed targets for the treatment of pain. Unfortunately, targeting these receptors therapeutically poses significant challenges including addiction, dependence, tolerance, and the appearance of side effects, such as respiratory depression and constipation. Moreover, misuse of prescription and illicit narcotics has resulted in the current opioid crisis. The mu-opioid receptor (MOR) is the cellular mediator of the effects of most commonly used opioids, and is a prototypical G protein-coupled receptor (GPCR) where new pharmacological, signalling and cell biology concepts have been coined. This review summarises the knowledge of the life cycle of this therapeutic …

Associations between the dopamine D4 receptor gene polymorphisms and personality traits in elite athletes.

2019

Personality traits and temperament may affect sports performance. Previous studies suggest that dopamine may play an important role in behavior regulation and physical exercise performance. The aim of this study is to determine associations between dopamine D4 receptor gene (DRD4 Ex3) polymorphisms and personality traits (such as neuroticism, extraversion, openness, agreeability and conscientiousness) in elite combat athletes. A total of 302 physically active, unrelated, self-reported Caucasian participants were recruited for this study. The participants consisted of 200 elite male combat athletes and 102 healthy male participants (control group). For personality trait measurements, the NEO…

Analysis of DRD2 Gene Polymorphism in the Context of Personality Traits in a Group of Athletes

2021

The presented study showed the relationship between dopamine receptor gene polymorphism and personality traits in athletes training in martial arts. Behavioral modulation resulting from a balance of the neurotransmitters dopamine and norepinephrine to inactivation of the dorsolateral prefrontal cortex and dysregulation of various pathways involved in attention and impulse control processes