scholarly journals A causal role for TRESK loss of function in migraine mechanisms

Brain ◽  
2019 ◽  
Vol 142 (12) ◽  
pp. 3852-3867 ◽  
Author(s):  
Philippa Pettingill ◽  
Greg A Weir ◽  
Tina Wei ◽  
Yukyee Wu ◽  
Grace Flower ◽  
...  
Keyword(s):  
Potassium Channel ◽  
Drug Target ◽  
Causal Role ◽  
Potential Drug Target ◽  
Potential Drug ◽  
Loss Of Function

The two-pore potassium channel TRESK is a potential drug target in pain and migraine. Pettingill et al. show that the F139WfsX2 mutation causes TRESK loss of function and hyperexcitability in nociceptors derived from iPSCs of patients with migraine. Cloxyquin, a TRESK activator, reverses migraine-relevant phenotypes in vitro and in vivo.

scholarly journals Biosynthesis of the redox cofactor mycofactocin comprises oligoglycosylation by MftF in Mycolicibacterium smegmatis

2019 ◽  
Author(s):  
Luis Peña-Ortiz ◽  
Ana Patrícia Graça ◽  
Huijuan Guo ◽  
Daniel Braga ◽  
Tobias G. Köllner ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Metabolic Profiling ◽  
Drug Target ◽  
Structure Elucidation ◽  
Potential Drug Target ◽  
Potential Drug ◽  
Alcohol Metabolism ◽  
Future Studies ◽  
Mycobacterial Diseases

AbstractMycofactocin (MFT) is a redox cofactor involved in alcohol metabolism of mycobacteria including Mycobacterium tuberculosis. In recent years, a preliminary biosynthetic model of MFT has been established by in-vitro studies, while the final structure of MFT remained elusive. Here, we report the discovery of MFT by metabolomics and establish a model of its biosynthesis in Mycolicibacterium smegmatis. Structure elucidation revealed that MFT is decorated with up to nine β-1,4-linked glucose residues. Dissection of biosynthetic genes demonstrated that the oligoglycosylation is catalyzed by the glycosyltransferase MftF. Furthermore, we confirm the cofactor function of MFT by activity-based metabolic profiling using the carveol dehydrogenase LimC and show that the MFT pool expands during cultivation on ethanol. Our results close an important gap of knowledge, will guide future studies into the physiological roles of MFT in bacteria and may inspire its utilization as a biomarker or potential drug target to combat mycobacterial diseases.

scholarly journals Phytochemicals and Potential Therapeutic Targets on Toxoplasma gondii Parasite

2020 ◽  
Vol 20 (9) ◽  
pp. 739-753
Author(s):  
Sharif Alhassan Abdullahi ◽  
Ngah Zasmy Unyah ◽  
Noshariza Nordin ◽  
Rusliza Basir ◽  
Wana Mohammed Nasir ◽  
...  
Keyword(s):  
Drug Target ◽  
Relevant Literature ◽  
Chemotherapeutic Agents ◽  
Potential Drug ◽  
Natural Sources ◽  
Drug Candidates ◽  
Target Sites ◽  
Phytochemical Compounds

Identification of drug target in protozoan T. gondii is an important step in the development of chemotherapeutic agents. Likewise, exploring phytochemical compounds effective against the parasite can lead to the development of new drug agent that can be useful for prophylaxis and treatment of toxoplasmosis. In this review, we searched for the relevant literature on the herbs that were tested against T. gondii either in vitro or in vivo, as well as different phytochemicals and their potential activities on T. gondii. Potential activities of major phytochemicals, such as alkaloid, flavonoid, terpenoids and tannins on various target sites on T. gondii as well as other related parasites was discussed. It is believed that the phytochemicals from natural sources are potential drug candidates for the treatment of toxoplasmosis with little or no toxicity to humans.

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