The polyQ diseases are caused by an abnormal expansion of the polyQ tract in the diseasecausing proteins. Proteins with an abnormally expanded polyQ stretch undergo a conformational transition to β-sheet rich structure, which assemble into insoluble aggregates with β-sheet rich amyloid fibrillar structures (Figure ) and accumulate as inclusion bodies in neurons, eventually leading to neurodegeneration. It has been thus suggested that polyQ diseases result from a toxic gain of function at the protein level, with a key pathological feature being the accumulation of aggregated polyQ proteins inside neurons nucleus and cytosol. However, while abnormal accumulation of the polyQ proteins such as inclusion bodies is one of the foremost pathological hallmarks commonly detected in the brains of the polyQ disease patients, the roles of aggregate/inclusion formation in disease pathogenesis have been controversial and remain one of the challenging problems in the field. Indeed, aggregates and inclusions are usually found in affected areas of the brain as compared to the unaffected ones, and the late onset and progressive nature of polyQ diseases matches the slow process of protein aggregation. Some researchers have suggested that oligomeric aggregates such as protofibrils and microaggregates are the immediate cause of polyQ toxicity and that large aggregates are in fact cytoprotective. A variety of cellular proteins, including molecular chaperones, cytoskeletal proteins, transcriptional factors and proteasomes, have been detected into the inclusion bodies, suggesting detrimental effects on a wide range of essential cellular functions, which possibly contribute to neuronal dysfunction and eventual neuronal loss in various regions of the brain.