A proteome-wide pipeline combining a highly parallel protein complementation assay (GluePCA) with the surface-based computational tool MaSIF-mimicry maps latent interactions between CRBN and molecular glue degraders, including substrates beyond canonical G-loop motifs. A screen of zinc finger constructs in yeast identified over 100 pomalidomide-dependent binders and 2 novel degrading constructs. The approach gives a scalable route to finding proteins already engaged by generic glues, the starting points for specific degraders.
The study shows that LRRK2's ROC GTPase acts as a nucleotide-dependent molecular switch that regulates its activation and autoinhibition, and reveals how some Parkinson's disease mutations disrupt this regulatory switch.
A team led by Zhang Rong and Bao Lei at Hebei Medical University published a study in Redox Biology describing engineered exosomes encapsulating miR-218-5p and modified with the iRGD targeting peptide, which significantly alleviated PM2.5-induced pulmonary fibrosis in mice when delivered by inhalation. In vitro experiments showed that exosomes secreted by PM2.5-exposed macrophages induced ferroptosis in epithelial cells, driving epithelial-mesenchymal transition, and targeted inhibition of HO-1 reversed this phenotype.
Why it matters: It demonstrates an inhaled engineered exosome strategy for delivering miRNA to inhibit ferroptosis, suggesting a potential therapy for environmentally induced pulmonary fibrosis.
