Insulin-Degrading Enzyme in the Fight against Alzheimer's Disease

After decades of research and clinical trials there is still no cure for Alzheimer's disease (AD). While impaired clearance of amyloid beta (Aβ) peptides is considered as one of the major causes of AD, it was recently complemented by a potential role of other toxic amyloidogenic species. Insulin-degrading enzyme (IDE) is the proteolytic culprit of various β-forming peptides, both extracellular and intracellular.

type: 
Journal Paper
journal: 
Trends in Pharmacological Sciences, 10 Nov 2017, doi : 10.1016/j.tips.2017.10.008
pubmed: 
29132916
Url: 
https://www.ncbi.nlm.nih.gov/pubmed/29132916
Impact Factor: 
12.797

Small molecules targeting the inactive form of the Mnk 1/2 kinases

Overexpression of the eukaryotic initiation factor 4E (eIF4E) is linked to a variety of cancers. Both mitogenactivated protein kinases-interacting kinases 1 and 2 (Mnk1/2) activate the oncogene eIF4E through posttranslational modification (phosphorylating it at the conserved Ser209). Inhibition of Mnk prevents eIF4E phosphorylation, making the Mnk−eIF4E axis a potential therapeutic target for oncology. Recently, the design and synthesis of a series of novel potent compounds inhibiting the Mnk1/2 kinases were carried out in-house.

type: 
Journal Paper
journal: 
ACS Omega 2017, 2, Pg 7881 - 7891, doi: 10.1021/acsomega.7b01403
Date of acceptance: 
2017-10-31

A yeast two-hybrid system for the screening and characterization of small-molecule inhibitors of protein–protein interactions identifies a novel putative Mdm2-binding site in p53

Background: Protein–protein interactions (PPIs) are fundamental to the growth and survival of cells and serve as excellent targets to develop inhibitors of biological processes such as host-pathogen interactions and cancer cell proliferation. However, isolation of PPI inhibitors is extremely challenging. While several in vitro assays to screen for PPI inhibitors are available, they are often expensive, cumbersome, and require large amounts of purified protein. In contrast, limited in vivo assays are available to screen for small-molecule inhibitors of PPI.

type: 
Journal Paper
journal: 
BMC Biology 2017 15:108, doi: 10.1186/s12915-017-0446-7
Url: 
https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-017-0446-7
Impact Factor: 
6.779
Date of acceptance: 
2017-10-19

High-throughput Prediction of Nephrotoxicity in Humans

The Lush Science Prize 2016 was awarded to Daniele Zink and Lit-Hsin Loo for the interdisciplinary
and collaborative work between their research groups in developing alternative methods for the
prediction of nephrotoxicity in humans. The collaboration has led to the establishment of a series of pioneering alternative methods for nephrotoxicity prediction, which includes: predictive gene expression
markers based on pro-inflammatory responses; predictive in vitro cellular models based on pluripotent

type: 
Journal Paper
journal: 
ATLA 45, Pg 241-252, 5 Nov 2017
Url: 
http://www.atla.org.uk/high-throughput-prediction-of-nephrotoxicity-in-humans/
Impact Factor: 
1.021

APD volumetric app: android app for the quantification of reagents

Quantifying reagents is a necessity in laboratory experiment planning but to do so with reasonable accuracy is a challenge when using unmarked containers. While there are volumetric measuring cylinders, the demand of sterility and purity in many experiments prevent their use in a feasible fashion. As a result, experienced estimation is usually relied upon, but this is fairly subjective, and may lead to large margins of error.

type: 
Journal Paper
journal: 
Scientific Phone Apps and Mobile Devices (2017) 3:7, doi: 10.1186/s41070-017-0019-8
Url: 
https://scientificphoneapps.springeropen.com/articles/10.1186/s41070-017-0019-8
Date of acceptance: 
2017-10-11

Evaluation of tools for long read RNA-seq splice-aware alignment

MOTIVATION:

type: 
Journal Paper
journal: 
Bioinformatics, 2017, Pg 1-7, doi: 10.1093/bioinformatics/btx668
pubmed: 
29069314
Url: 
https://www.ncbi.nlm.nih.gov/pubmed/29069314
Impact Factor: 
7.037
Date of acceptance: 
2017-10-18

A New Generation of Arachidonic Acid Analogues as Potential Neurological Agent Targeting Cytosolic Phospholipase A2

Cytosolic phospholipase A2 (cPLA2) is an enzyme that releases arachidonic acid (AA) for the synthesis of eicosanoids and lysophospholipids which play critical roles in the initiation and modulation of oxidative stress and neuroinflammation. In the central nervous system, cPLA2 activation is implicated in the pathogenesis of various neurodegenerative diseases that involves neuroinflammation, thus making it an important pharmacological target. In this paper, a new class of arachidonic acid (AA) analogues was synthesized and evaluated for their ability to inhibit cPLA2.

type: 
Journal Paper
journal: 
Scientific Reports 7, Article no: 13684, 2017, doi:10.1038/s41598-017-13996-8
Url: 
https://www.nature.com/articles/s41598-017-13996-8
Impact Factor: 
4.259
Date of acceptance: 
2017-10-05

EZH2 promotes neoplastic transformation through VAV interaction-dependent extranuclear mechanisms

Recently, we reported that the histone methyltransferase, EZH2, controls leukocyte migration through interaction with the cytoskeleton remodeling effector, VAV, and direct methylation of the cytoskeletal regulatory protein, Talin. However, it is unclear whether this extranuclear, epigenetic-independent function of EZH2 has a profound impact on the initiation of cellular transformation and metastasis. Here, we show that EZH2 increases Talin1 methylation and cleavage, thereby enhancing adhesion turnover and promoting accelerated tumorigenesis.

type: 
Journal Paper
journal: 
Oncogene 2017, Pg 1-17, doi:10.1038/onc.2017.309
pubmed: 
28967906
Url: 
http://www.nature.com.ejproxy.a-star.edu.sg/articles/onc2017309
Impact Factor: 
7.519
Date of acceptance: 
2017-07-11

Novel insights into the vancomycin-resistant Enterococcus faecalis (V583) alkylhydroperoxide reductase subunit F

The ability of the vancomycin-resistant Enterococcus faecalis (V583) to restore redox homeostasis via antioxidant defense mechanism is of importance, and knowledge into this defense is essential to understand its antibiotic-resistance and survival in hosts. The flavoprotein disulfide reductase AhpR, composed of the subunits AhpC and AhpF, represents one such vital part. Circular permutation was found to be a feature of the AhpF protein family. E.

type: 
Journal Paper
journal: 
Biochimica et Biophysica Acta (BBA), 2017 Sep 19, doi: 10.1016/j.bbagen.2017.09.011
pubmed: 
28935609
Url: 
https://www.ncbi.nlm.nih.gov/pubmed/28935609
Impact Factor: 
4.702
Date of acceptance: 
2017-09-15

Prenylation of Viral Proteins by Enzymes of the Host: Virus-Driven Rationale for Therapy With Statins and FT/GGT1 Inhibitors

Intracellular bacteria were recently shown to employ eukaryotic prenylation system for modifying activity and ensuring proper intracellular localization of their own proteins. Following the same logic, the proteins of viruses may also serve as prenylation substrates.

type: 
Journal Paper
journal: 
BioEssays, 2017 Oct;39(10). doi: 10.1002/bies.201700014
pubmed: 
28885709
Url: 
https://www.ncbi.nlm.nih.gov/pubmed/28885709
Impact Factor: 
4.441
Syndicate content