![]() ![]() This method of study is limited in that it represents the end-stages of the disease ( Marchetto et al., 2010 Marchetto et al., 2011). Initial insight regarding the neuropathology of HD was identified in post-mortem brain tissue from human HD patients ( DiFiglia, 1997 Sapp et al., 1997). GABAergic and parvalbuminergic striatal projection neurons are also severely affected ( Hedreen and Folstein, 1995). During the symptomatic phase of HD, the external segment of the globus pallidus, the substantia nigra pars reticulata, and the substantia nigra pars compacta are severely degenerated ( Deng et al., 2004). A loss of enkephalinergic neurons in the external segment of the globus pallidus is also typical of presymptomatic HD ( Deng et al., 2004). Nuclear inclusions of HTT in striatal neurons actually precede symptom onset ( Laforet et al., 2001). The hallmark of HD is neurodegeneration, predominantly in the striatum and cortex ( Sapp et al., 1997). Throughout the literature, a number of strategies have been used to uncover the pathology of HD and other neurological disorders. The mechanisms placing these specific neuron populations at risk is a critical question. Studies suggest that the aggregation of mutant HTT fragments is the major cause of toxicity, specifically damaging cortical and striatal medium spiny neurons in HD patients ( Davies and Ramsden, 2001 Li and Li, 2006 Gil and Rego, 2008 Imarisio et al., 2008 Ross and Shoulson, 2009 Sassone et al., 2009 Johnson and Davidson, 2010). Existing treatments are aimed at the alleviation of symptoms, however, therapies that slow or reverse disease progression have yet to be implemented. Currently HD is a fatal diagnosis for which there is no cure. Individuals with repeats of ≥ 40 units are at risk of developing HD as their lives progress ( Li and Li, 2006 Gil and Rego, 2008). In general populations the repeat average is less than 36 units. HD on estimate affects 7–10 per 100,000 individuals and is most prevalent in population of European origin ( Gil and Rego, 2008). The mutation produces a stretch of glutamine residues spanning the N-terminus of the Huntingtin protein (HTT). The disease is caused by an unstable expansion of CAG repeats in the coding region of the Huntingtin gene IT15 ( MacDonald et al., 1993). Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder. We also highlight the prospective application of Huntington’s disease stem cell models in the development of novel therapeutic strategies and advancement of personalized medicine. In this article we review current stem cell models that have been reported, as well as discuss the issues that impair these studies. Although some progress has been made, there are a number of challenges and limitations that must be overcome before the true potential of this research strategy is achieved. ![]() A number of stem cell derived models have been employed to establish in vitro research models of Huntington’s disease that can be used to investigate cellular pathology and screen for drug and cell-based therapies. Several advantages of using a stem cell model include the potential for cells to derive disease relevant neuronal cell types, providing a system for researchers to monitor disease progression during neurogenesis, along with serving as a platform for drug discovery. ![]() ![]() Pluripotent cellular models have shown great promise in the study of a number of neurological disorders. ![]()
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