A Supramolecular Transition Underlies the Pathogenic Threshold in Polyglutamine Disease

Polyglutamine (polyQ) diseases are neurodegenerative disorders caused by CAG repeat expansions and are characterized by a clinical pathogenic threshold typically observed between 35 and 39 glutamine residues. While this threshold is well established from genetic and clinical studies, its molecular and thermodynamic origin remains unclear. Here, we performed all-atom molecular dynamics (MD) simulations and transcriptome analysis to investigate polyQ assemblies spanning the pathological transition