Molecular pathogenesis of the polyQ diseases and the therapeutic target of QBP1. Proteins with an expanded polyQ stretch are prone to misfold into a β-sheet dominant structure, leading to their assembly into oligomers and amyloid fibrillar aggregates, followed by their accumulation as inclusion bodies within neurons, eventually resulting in neurodegeneration. The peptide QBP1 inhibits the initial misfolding into a β-sheet dominant structure of the protein by binding to the expanded polyQ stretch, resulting in suppression of polyQ protein aggregation and polyQ-induced neurodegeneration. Question marks indicate structures for which cytotoxicity remains controversial.