In the initial studies exploring the molecular mechanisms of aggregate formation from the monomeric form of the expanded polyQ proteins it has been shown that synthetic polyQ peptides with a relatively short glutamine repeat of ~15 form aggregates with β-sheet rich structures under certain conditions. PolyQ peptides with longer glutamine repeats gradually undergo a conformational change from a soluble random coil structure to insoluble amyloid-like fibrils with β-sheet structures. Intermediate structures such as oligomers and protofibrils are produced before amyloid formation, structurally similar to those of amyloid-β and α-synuclein formed in Alzheimer's and Parkinson's diseases, implying a shared pathogenic mechanism among the neurodegenerative diseases associated with protein aggregation. Therefore, the proposed aggregation cascade of the expanded polyglutamine (polyQ) proteins includes a conformational transition from the native conformer to the β-sheet rich structure in a monomeric state, which assembles into oligomers and insoluble aggregates with amyloid fibrillar structures, potentially leading to accumulation as intracellular inclusions (Figure ).