A team of neurodegenerative disease researchers has ascertained a molecular mechanism that hinders or reverses the formation of insoluble protein aggregates that suffuse sundry brain disorders, including front temporal dementia (FTD) and amyotrophic lateral sclerosis (ALS).Members of the class of RNA-binding proteins (RBPs) with prion-like domains (PrLDs) experience a phase transition to a functional liquid form. In this form, RBPs can mature into abnormal hydrogels composed of pathological fibrils that underpin fatal neurodegenerative disorders. The investigators added NIRs to aggregates of TDP-43 and FUS proteins.
NIRs also dissolved cytoplasmic clumps in cells, and functional RBPs were returned to the nucleus.
said senior author Dr. James Shorter, associate professor of biochemistry and biophysics at the University of Pennsylvania. “We want to reverse the formation of these clumps and put the RNA-binding proteins back in their proper place, inside the nucleus”. Furthermore, several nuclear RBPs with PrLDs, including TDP-43, FUS, hnRNPA1, and hnRNPA2, mistakenly associate with cytoplasmic inclusions in neurodegenerative disorders, and mutations in their PrLDs can accelerate fibril formation and cause disease.
Original Link:https://www.biotechdaily.com/genomics-proteomics/articles/294773402/protein-droplets-stimulate-neurodegenerative-fibril-clumping.html