Biophysicists from the MIPT Center for Molecular Mechanisms of Aging and Age-Related Diseases have teamed up with colleagues from Canada, the U.S., Japan, France, and Germany to shed light on the structure and functioning mechanism of the CysLT receptors, which regulate inflammatory responses associated with allergic disorders. Their findings are reported in Nature Communications.
[...] As of today, the development of more effective medications for asthma and associated conditions is hindered by the lack of information on how and to what ligands the CysLT receptors bind. Their functioning mechanisms have not been clearly understood either, as this requires high-resolution structural biology data. Once these are available, researchers can proceed using computer simulations.
[...] In their recent study, researchers from the Moscow Institute of Physics and Technology identified the most critical ligand-binding determinants of the CysLT1 and CysLT2 receptors based on the structural analysis the team performed for CysLT2R and the structural data on CysLT1R published by the laboratory in October.
"The new structures have greatly improved the accuracy of ligand docking and helped us better understand the properties of ligands with respect to both receptors. Now we know how to alter drug design templates to inhibit the activity of both the CysLT1 and CysLT2 receptors or do that selectively for either of them," commented Anastasiia Gusach , a Ph.D. student at MIPT and a junior researcher at the MIPT Laboratory of Structural Biology of G Protein-Coupled Receptors.
In the future, these structures could be further developed to serve as drug candidates or tool compounds, aiding in understanding the specific role of each of the CysLT receptor subtypes in various physiological and pathological processes.
[...] This implies that with the rapid development of genome sequencing technologies and the accumulation of large volumes of statistical data, structure-function studies will not only allow accurate prediction of disease for every patient but will also enable predicting drug efficacy and improving patient safety based on how these variations in genes affect the response to certain medications.
More information: Anastasiia Gusach et al. Structural basis of ligand selectivity and disease mutations in cysteinyl leukotriene receptors, Nature Communications (2019). DOI: 10.1038/s41467-019-13348-2
(Score: 0) by Anonymous Coward on Monday January 27 2020, @12:25AM (1 child)
> "Asthma is most often relieved by bowel tolerance doses of ascorbate. A child regularly having asthmatic attacks following exercise is usually relieved of these attacks by large doses of ascorbate. So far all of my patients having asthmatic attacks associated with the onset of viral diseases have been ameliorated by this treatment."
https://www.ncbi.nlm.nih.gov/pubmed/7321921 [nih.gov]
> "A systematic review found three studies providing direct information on vitamin C and common cold-induced asthma [6]. An RCT in Nigeria examined patients whose asthma exacerbations resulted from respiratory infections. Vitamin C at a dosage of 1 g/day lowered the incidence of severe and moderate asthma attacks by 89% (52% to 98%; based on 3/22 vs. 23/19). An RCT in former East Germany on patients with infection-related asthma found that 5 g/day of vitamin C decreased the prevalence of bronchial hypersensitivity to histamine by 52 percentage points (25 to 71 pp; decrease in prevalence from 91% to 39%). The third study compared participants while they suffered from the common cold and after they had recovered. While they suffered from the cold, vitamin C raised histamine PC20 levels 3.2-fold, thereby reducing bronchial hypersensitivity
[...]
Cochrane review on vitamin C and asthma was published in 2001 [9] and it was updated in 2004 and 2009. In 2009, I pointed out that the Cochrane review contained substantial errors in the data extraction and analysis [10]. The authors replied to my criticism in 2012 and even then their reply was loaded with of errors [11]. With the first version published in 2001, the sloppy Cochrane review misled readers about the evidence on vitamin C and asthma for a decade."
https://www.bmj.com/content/349/bmj.g5517/rr/797361 [bmj.com]
(Score: 0) by Anonymous Coward on Monday January 27 2020, @12:46AM
> Plasma ascorbic acid was lower in severe (31.9±3.6 µM) compared with mild-to-moderate asthmatic (52.3±2.6) or control subjects (52.7±2.9).
https://www.ncbi.nlm.nih.gov/pubmed/16055873 [nih.gov]