N-Myristoylation as a Drug Target in Malaria: Exploring the Role of N-Myristoyltransferase Substrates in the Inhibitor Mode of Action

2018 ◽  
Vol 4 (4) ◽  
pp. 449-457 ◽  
Author(s):  
Anja C. Schlott ◽  
Anthony A. Holder ◽  
Edward W. Tate
Keyword(s):  
Author(s):  
Delphine Ji ◽  
Zheng-wei Luo ◽  
Andrea Ovcjak ◽  
Rahmah Alanazi ◽  
Mei-Hua Bao ◽  
...  
Keyword(s):  

Animals ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 2167
Author(s):  
Ehsan Ahmadifar ◽  
Hamideh Pourmohammadi Fallah ◽  
Morteza Yousefi ◽  
Mahmoud A. O. Dawood ◽  
Seyed Hossein Hoseinifar ◽  
...  

The crucial need for safe and healthy aquatic animals obligates researchers in aquaculture to investigate alternative and beneficial additives. Medicinal herbals and their extracts are compromised with diverse effects on the performances of aquatic animals. These compounds can affect growth performance and stimulate the immune system when used in fish diet. In addition, the use of medicinal herbs and their extracts can reduce oxidative stress induced by several stressors during fish culture. Correspondingly, aquatic animals could gain increased resistance against infectious pathogens and environmental stressors. Nevertheless, the exact mode of action where these additives can affect aquatic animals’ performances is still not well documented. Understanding the mechanistic role of herbal supplements and their derivatives is a vital tool to develop further the strategies and application of these additives for feasible and sustainable aquaculture. Gene-related studies have clarified the detailed information on the herbal supplements’ mode of action when administered orally in aquafeed. Several review articles have presented the potential roles of medicinal herbs on the performances of aquatic animals. However, this review article discusses the outputs of studies conducted on aquatic animals fed dietary, medicinal herbs, focusing on the gene expression related to growth and immune performances. Furthermore, a particular focus is directed to the expected influence of herbal supplements on the reproduction of aquatic animals.


2021 ◽  
Vol 9 (4) ◽  
pp. 826
Author(s):  
Dorien Mabille ◽  
Camila Cardoso Santos ◽  
Rik Hendrickx ◽  
Mathieu Claes ◽  
Peter Takac ◽  
...  

Human African trypanosomiasis is a neglected parasitic disease for which the current treatment options are quite limited. Trypanosomes are not able to synthesize purines de novo and thus solely depend on purine salvage from the host environment. This characteristic makes players of the purine salvage pathway putative drug targets. The activity of known nucleoside analogues such as tubercidin and cordycepin led to the development of a series of C7-substituted nucleoside analogues. Here, we use RNA interference (RNAi) libraries to gain insight into the mode-of-action of these novel nucleoside analogues. Whole-genome RNAi screening revealed the involvement of adenosine kinase and 4E interacting protein into the mode-of-action of certain antitrypanosomal nucleoside analogues. Using RNAi lines and gene-deficient parasites, 4E interacting protein was found to be essential for parasite growth and infectivity in the vertebrate host. The essential nature of this gene product and involvement in the activity of certain nucleoside analogues indicates that it represents a potential novel drug target.


2021 ◽  
Vol 31 (1) ◽  
Author(s):  
Thomas Thiebault ◽  
Laëtitia Fougère ◽  
Anaëlle Simonneau ◽  
Emilie Destandau ◽  
Claude Le Milbeau ◽  
...  

AbstractThis study investigated the potential of sediments accumulated in sewer systems to record human activities through the occurrence of drug target residues (DTR). The installation studied is 17 m deep underground decantation tank that traps the coarse fractions of a unitary sewer system (northern part of Orléans, France), collecting both stormwater and wastewater. The sediments deposited in this tank could constitute a nonesuch opportunity to study the historical evolution of illicit and licit drug consumption in the catchment, however, the deposition processes and the record of DTRs remain largely unknown at present. Five cores were acquired from 2015 to 2017. One hundred fifty-two sediment samples were extracted using a mixture of ultra-pure water:methanol (1:1) prior to analysis of the extracts by high-pressure liquid chromatography coupled to tandem mass spectrometry. Several classical sedimentological analyses such as total organic carbon, facies description and granulometry were also performed on these samples, in order to understand the most important factors (e.g., physico-chemical properties of the DTRs, solid type, assumed load in wastewater) impacting their deposition.The key role of the speciation of DTRs was highlighted by the higher contents in neutral and anionic DTRs in organic layers, whereas only cationic DTRs were found in mineral layers. The considerable modifications in the sediments’ properties, generated by distinct origins (i.e., stormwater or wastewater), are therefore the most important drivers that must be taken into account when back-calculating the historical patterns of drug consumption from their DTR concentrations in decantation tank sediments. Further research remains necessary to fully understand the deposition process, but this study provides new clues explaining these temporal evolutions.


RSC Advances ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 2453-2461
Author(s):  
Min-Che Tung ◽  
Keng-Chang Tsai ◽  
Kit-Man Fung ◽  
Ming-Jaw Don ◽  
Tien-Sheng Tseng

The cytosolic non-receptor protein kinase, spleen tyrosine kinase (SYK), is an attractive drug target in autoimmune, inflammatory disorder, and cancers indications.


Open Biology ◽  
2014 ◽  
Vol 4 (2) ◽  
pp. 130217 ◽  
Author(s):  
Puneet Sharma ◽  
Alo Nag

The ability of cullin 4A (CUL4A), a scaffold protein, to recruit a repertoire of substrate adaptors allows it to assemble into distinct E3 ligase complexes to mediate turnover of key regulatory proteins. In the past decade, a considerable wealth of information has been generated regarding its biology, regulation, assembly, molecular architecture and novel functions. Importantly, unravelling of its association with multiple tumours and modulation by viral proteins establishes it as one of the key proteins that may play an important role in cellular transformation. Considering the role of its substrate in regulating the cell cycle and maintenance of genomic stability, understanding the detailed aspects of these processes will have significant consequences for the treatment of cancer and related diseases. This review is an effort to provide a broad overview of this multifaceted ubiquitin ligase and addresses its critical role in regulation of important biological processes. More importantly, its tremendous potential to be exploited for therapeutic purposes has been discussed.


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