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iPS cells in the study of PD molecular pathogenesis

Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disease and its pathogenic mechanisms are poorly understood. The majority of PD cases are sporadic but a number of genes are associated with familial PD. Sporadic and familial PD have many molecular and cellular features in common, suggesting some shared pathogenic mechanisms. Induced pluripotent stem cells (iPSCs) have been derived from patients harboring a range of different mutations of PD-associated genes. PD patient-derived iPSCs have been differentiated into relevant cell types, in particular dopaminergic neurons and used as a model to study PD. In this review, we describe how iPSCs have been used to improve our understanding of the pathogenesis of PD. We describe what cellular and molecular phenotypes have been observed in neurons derived from iPSCs harboring known PD-associated mutations and what common pathways may be involved.

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Fig. 1

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Correspondence to Steven Finkbeiner.

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This review is supported by the Michael J Fox Foundation, Gladstone Institutes, NIH U54 HG008105, R01 NS039074 and R01 NS083390

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Cobb, M.M., Ravisankar, A., Skibinski, G. et al. iPS cells in the study of PD molecular pathogenesis. Cell Tissue Res 373, 61–77 (2018). https://doi.org/10.1007/s00441-017-2749-y

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Keywords

  • Induced pluripotent stem cell (iPSC)
  • Parkinson’s disease
  • Autophagy
  • Alpha-synuclein
  • Neurodegeneration