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Li et al. 2005 , 2008 ; Patani et al. 2011 ; Perrier et al. 2004 ; Perrier and Peschanski
2012 ; Sánchez-Danés et al. 2012 ; Shi et al. 2012 ; Yan et al. 2005 ). Among the cer-
ebellar diseases, the cerebellar ataxia is a diverse group of neurological disorders,
defined by a loss of motor coordination that results from the degeneration of specific
populations of neurons in the cerebellar cortex (predominantly Purkinje cell), brain-
stem, and spinocerebellar tracts (Klockgether 2011 ; Manto and Marmolino 2009 ).
Purkinje cells, whose large soma, extensive fan-shaped dendritic tree, and charac-
teristic electrophysiological properties (as described herein below) render them par-
ticularly vulnerable to proteostatic insults and disturbances in ion channel function
caused by mutations in spinocerebellar ataxia disease genes (Hekman and Gomez
2014 ). Disease models using patient-derived iPSCs for neurodegenerative disease,
including amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), spinal
muscular atrophy (SMA), Alzheimer’s disease (AD), and Huntington’s disease
(HD), have extensively studied for understanding disease mechanisms and develop-
ing therapies. However few studies on iPSC-derived models of cerebellar diseases
have been reported (Bird et al. 2014 ; Eigentler et al. 2013 ; Hick et al. 2013 ; Koch
et al. 2011 ; Ku et al. 2010 ). To date, these studies still remain at the level of the
generation of disease-specific iPSCs or, at most, generation of iPSC-derived ßIII-
tubulin positive neurons. While the analyses with patient-derived iPSCs or neurons
differentiated from them may provide some insights into the pathogenesis of the
cerebellar diseases, they cannot directly assay the functions and dysfunctions that
are specific to mature cerebellar neurons. Recapitulation of accurate phenotypes of
patients in vitro with patient-derived cerebellar neurons would provide much more
information and be crucial for understanding the cerebellar diseases. It is important
to generate specific neuronal subtypes for construction of the disease models (Inoue
et al. 2014 ; Watson et al. 2015 ; Wiethoff et al. 2015 ). We are currently establishing
the culture systems for generating the various cerebellar cell types from human
iPSCs. Recently, we have succeeded in the generation of Purkinje cells from
disease- specific iPSC (Muguruma et al. 2015 ; Morino et al. 2015 ). Our efficient
culture protocol is going to be widely used by other groups as it was used in a recent
report (Wang et al. 2015 ). Thus, the combination of the generation of patient-derived
iPSCs and the differentiation of them into mature cerebellar neurons will lead to the
establishment of disease models that accelerate the development of effective thera-
pies against the human cerebellar diseases. Although only a few therapies are effec-
tive to the cerebellar diseases, disease-specific iPSC research should provide us new
knowledge to overcome these diseases.
2.4 Conclusion
Disease modeling using patient-derived iPSCs is likely to provide significant
insights to study of neurodegenerative disease, including the inherited and sporadic
cerebellar ataxia. In particular, human iPSCs-derived Purkinje cells should provide
us useful information on the developmental mechanisms, pathological processes,
K. Muguruma