Polyglutamine (polyQ) diseases are a group of inherited neurodegenerative disorders caused by expanded cytosine-adenine-guanine (CAG) repeats encoding proteins with abnormally expanded polyglutamine tract. A total of nine polyQ disorders have been identified, including Huntington\'s disease, six spinocerebellar ataxias, dentatorubral pallidoluysian atrophy (DRPLA), and spinal and bulbar muscular atrophy (SBMA). The diseases of this class are each considered rare, yet polyQ diseases constitute the largest group of monogenic neurodegenerative disorders. While each subtype of polyQ diseases has its own causative gene, certain pathologic molecular attributes have been implicated in virtually all of the polyQ diseases, including protein aggregation, proteolytic cleavage, neuronal dysfunction, transcription dysregulation, autophagy impairment, and mitochondrial dysfunction. Although animal models of polyQ disease are available helping to understand their pathogenesis and access disease-modifying therapies, there is neither a cure nor prevention for these diseases, with only symptomatic treatments available. In this paper, we analyze data from the CAS Content Collection to summarize the research progress in the class of polyQ diseases. We examine the publication landscape in the area in effort to provide insights into current knowledge advances and developments. We review the most discussed concepts and assess the strategies to combat these diseases. Finally, we inspect clinical applications of products against polyQ diseases with their development pipelines. The objective of this review is to provide a broad overview of the evolving landscape of current knowledge regarding the class of polyQ diseases, to outline challenges, and evaluate growth opportunities to further efforts in combating the diseases.

The dominantly-inherited ataxias characterised by expanded polyglutamine tracts-spinocere bellar ataxias (SCAs) 1, 2, 3, 6, 7, 17, dentatorubral pallidoluysian atrophy (DRPLA) and, in part, SCA 8-have all been shown to result in various degrees of cognitive impairment. We survey the literature on the cognitive consequences of each disorder, attempting correlation with their published neuropathological, magnetic resonance imaging (MRI) and clinical features. We suggest several psychometric instruments for assessment of executive function, whose results are unlikely to be confounded by visual, articulatory or upper limb motor difficulties. Finally, and with acknowledgement of the inadequacies of the literature to date, we advance a tentative classification of these disorders into three groups, based on the reported severity of their cognitive impairments, and correlated with their neuropathological topography and MRI findings: group 1-SCAs 6 and 8-mild dysexecutive syndrome based on disruption of cerebello-cortical circuitry; group 2-SCAs 1, 2, 3, and 7-more extensive deficits based largely on disruption of striatocortical in addition to cerebello-cerebral circuitry; and group 3-SCA 17 and DRPLA-in which cognitive impairment severe enough to cause a dementia syndrome is a frequent feature.