Readable research linked to original sources
Articles
Browse normalized, publication-ready research with direct links to its evidence and source.
Loading articles data…
Readable research linked to original sources
Browse normalized, publication-ready research with direct links to its evidence and source.
Loading articles data…
Readable research linked to original sources
Browse normalized, publication-ready research with direct links to its evidence and source.
16 articles
Newest firstCannabinoid receptor 1 (CB1) is a G protein-coupled receptor that regulates critical physiological processes including pain, appetite, and cognition. Understanding the conformational dynamics of CB1 associated with transitions between inactive and active signaling states is imperative for developing targeted modulators. Using microsecond-level all-atom molecular dynamics simulations, we identified marked differenc…
Open article record in new tab ↗In the last years, the connection between the endocannabinoid system (eCS) and neuroprotection has been discovered, and evidence indicates that eCS signaling is involved in the regulation of cognitive processes and in the pathophysiology of Alzheimer's disease (AD). Accordingly, pharmacotherapy targeting eCS could represent a valuable contribution in fighting a multifaceted disease such as AD, opening a new perspe…
Open article record in new tab ↗Δ9-tetrahydrocannabinol (Δ9-THC), the main active ingredient of Cannabis sativa (marijuana), interacts with the human brain cannabinoid (CB1) receptor and mimics pharmacological effects of endocannabinoids (eCBs) like N-arachidonylethanolamide (AEA). Due to its flexible nature of AEA structure with more than 15 rotatable bonds, establishing its binding mode to the CB1 receptor is elusive. The aim of the present st…
Open article record in new tab ↗The CB1 cannabinoid receptor is a G-protein coupled receptor highly expressed throughout the central nervous system that is a promising target for the treatment of various disorders, including anxiety, pain, and neurodegeneration. Despite the wide therapeutic potential of CB1, the development of drug candidates is hindered by adverse effects, rapid tolerance development, and abuse potential. Ligands that produce b…
Open article record in new tab ↗Cellobiohydrolases directly convert crystalline cellulose into cellobiose and are of biotechnological interest to achieve efficient biomass utilization. As a result, much research in the field has focused on identifying cellobiohydrolases that are very fast. Cellobiohydrolase A from the bacterium Cellulomonas fimi (CfCel6B) and cellobiohydrolase II from the fungus Trichoderma reesei (TrCel6A) have similar catalyti…
The binding pockets of odorant binding proteins from Anopheles gambiae (OBP1 and OBP47) were analysed using in silico modelling. The feasibility of creating mutant proteins to achieve a protein array capable of detecting drugs of abuse in solution or in vapour phase was investigated. OBP1 was found to be easily adapted and several mutant proteins were expressed and characterised. AgamOBP1_S82P was found to have hi…
Open article record in new tab ↗Cannabigerol (CBG) and cannabichromene (CBC) are non-psychoactive cannabinoids that have raised increasing interest in recent years. These compounds exhibit good tolerability and low toxicity, representing promising candidates for drug repositioning. To identify novel potential therapeutic targets for CBG and CBC, an integrated ligand-based and structure-based study was performed. The results of the analysis led t…
Open article record in new tab ↗The endocannabinoid system has emerged as a promising target for the treatment of numerous diseases, including cancer, neurodegenerative disorders, and metabolic syndromes. Thus far, two cannabinoid receptors, CB1 and CB2, have been discovered, which are found predominantly in the central nervous system (CB1) or the immune system (CB2), among other organs and tissues. CB1 receptor ligands have been shown to induce…
Open article record in new tab ↗Pathological tau aggregates in Alzheimer's disease (AD) and frontotemporal lobar degeneration-tau (FTLD-tau) adopt distinct conformations differentiated by the AD-tau specific monoclonal antibody (mAb) GT-38 that are not readily visualized using phosphorylation-specific anti-tau mAbs. To determine the extent of co-morbid AD-tau pathology in FTLD-tau, we performed immunohistochemical (IHC) staining with GT-38 and a…
Intracellular filamentous tau pathology is the defining feature of tauopathies, which form a subset of neurodegenerative diseases. We have analyzed pathological tau in Alzheimer's disease, and in frontotemporal lobar degeneration associated with tauopathy to include cases with Pick bodies, corticobasal degeneration, progressive supranuclear palsy, and ones due to intronic mutations in MAPT. We found that the C-ter…
Open article record in new tab ↗Background Fatty acid amide hydrolase 2 (FAAH2) is a hydrolase that mediates the degradation of endocannabinoids in man. Alterations in the endocannabinoid system are associated with a wide variety of neurologic and psychiatric conditions, but the phenotype and biochemical characterization of patients with genetic defects of FAAH2 activity have not previously been described. We report a male with autistic features…
During the asymmetric division of Drosophila neuroblasts (NBs), the scaffold Miranda (Mira) coordinates the subcellular distribution of cell-fate determinants including Staufen (Stau) and segregates them into the ganglion mother cells (GMCs). Here we show the fifth double-stranded RNA (dsRNA)-binding domain (dsRBD5) of Stau is necessary and sufficient for binding to a coiled-coil region of Mira cargo-binding domai…
Protein Kinase A (PKA) is the major receptor for the cyclic adenosine monophosphate (cAMP) secondary messenger in eukaryotes. cAMP binds to two tandem cAMP-binding domains (CBD-A and -B) within the regulatory subunit of PKA (R), unleashing the activity of the catalytic subunit (C). While CBD-A in RIα is required for PKA inhibition and activation, CBD-B functions as a "gatekeeper" domain that modulates the control…
A 3D-QSAR (CoMFA) study was performed in an extensive series of aminoalkylindoles derivatives with affinity for the cannabinoid receptors CB1 and CB2. The aim of the present work was to obtain structure-activity relationships of the aminoalkylindole family in order to explain the affinity and selectivity of the molecules for these receptors. Major differences in both, steric and electrostatic fields were found in…
To find whether the plasma fibronectin (FN) molecular status can be useful to differentiate between rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). The expression of plasma FN domains was determined by ELISA using monoclonal domain-specific antibodies. FN molecular forms were revealed by immunoblotting and analyzed by densitometry. The following findings were found: (1) Mean values of (Fibrin-Hep…
Open article record in new tab ↗A series of novel 2-pyridylbenzimidazole derivatives was rationally designed and synthesized based on our previous studies on benzimidazole 14, a CB1 agonist used as a template for optimization. In the present series, 21 compounds displayed high affinities with Ki values in the nanomolar range. JM-39 (compound 39) was the most active of the series (KiCB1 = 0.53 nM), while compounds 31 and 44 exhibited similar affi…