Pharmacology & Biotechnology
TPC2 promotes choroidal angiogenesis and inflammation in a mouse model of neovascular age-related macular degenerationThis study identifies the endolysosomal two-pore channel TPC2 as a potential novel drug target for age-related macular degeneration (AMD). Inhibition of TPC2 reduces two key clinical hallmarks of the AMD, retinal inflammation and formation of leaky choroi.
BRD2 regulation of sigma-2 receptor upon cholesterol deprivationUpon cholesterol deprivation, epigenetic bookmark reader BRD2 and master transcription factor SREBP2 form a complex at bookmarked chromatin (H3K27ac), thereby activating the transcription of the sigma-2 receptor—a recently unveiled player in cholesterol homeostasis.
The stress polarity signaling (SPS) pathway serves as a marker and a target in the leaky gut barrier: implications in aging and cancerUsing patient-derived organoids the authors show how a specialized polarity pathway protects our gut barrier from stress-induced collapse. Findings highlight both diagnostic and therapeutic potential of the pathway for treating gut barrier dysfunction in aging, cancer, and dysbiosis.
Phenotypic proteomic profiling identifies a landscape of targets for circadian clock–modulating compoundsThis study provides comprehensive insights into the mechanism of action and cellular effects of circadian period–modulating compounds, which is critical for clearly defining molecular targets to modulate daily rhythms for therapeutic benefit.
ADAPTABLE: a comprehensive web platform of antimicrobial peptides tailored to the user’s researchADAPTABLE is a webserver and database of antimicrobial peptides that uses sequence and property alignment to highlight their mode of action against the threat of resistance in medicine and agriculture.
Engineering Photorhabdus luminescens toxin complex (PTC) into a recombinant injection nanomachineThe article shows successful engineering of the syringe-like injection apparatus of Photorhabdus luminescens as standalone nanomachine for delivery of protein toxins and enzymes from different species into mammalian cells.
A molecule inducing androgen receptor degradation and selectively targeting prostate cancer cellsA new molecule induces AR sumoylation and degradation resulting in selective growth inhibition in AR-dependent prostate cancer cells, but its activity is blunted by interference with proteasomes.
Tamoxifen blocks retrograde trafficking of Shiga toxin 1 and 2 and protects against lethal toxicosisThis study reports an unexpected role of late endosome–lysosome fusion in early endosome-to-Golgi trafficking of Shiga toxins and identifies tamoxifen to be a potent inhibitor of Shiga toxicosis.
Vamorolone targets dual nuclear receptors to treat inflammation and dystrophic cardiomyopathyVamorolone is a first-in-class dissociative drug that selectively targets the glucocorticoid receptor to safely treat chronic inflammation and the mineralocorticoid receptor to treat cardiomyopathy, providing efficacy with improved safety in mouse models of Duchenne muscular dystrophy.