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Parkinson's disease (PD) is the second most common neurodegenerative disease, with a strong genetic component to both the familial and sporadic forms. The cardinal motor symptoms of the disease result from the loss of dopamine (DA) neurons in the midbrain. There is currently no cure for PD and improved methods for modelling the disease are required in order to develop more effective therapeutic interventions. Patient-derived induced pluripotent stem cells (iPSCs) carry the genetic background of the donor, enabling accurate modelling of genetic diseases in vitro. Various human iPSCs from patients suffering different genetic forms of PD have been differentiated into DA neurons and demonstrated signs of the pathophysiology of PD in vitro. The examination of key cellular pathways such as calcium regulation and autophagy indicate that disease-associated genetic variants may have important implications for cellular function. This review examines and critiques how DA neurons from patient iPSCs have been used to model PD in vitro, and what iPSCs might hold for the future of PD research. This article is part of the Special Issue entitled 'The Synaptic Basis of Neurodegenerative Disorders'.

Original publication

DOI

10.1016/j.neuropharm.2013.08.035

Type

Journal article

Journal

Neuropharmacology

Publication Date

01/2014

Volume

76 Pt A

Pages

88 - 96

Keywords

Alpha synuclein, CMA, DA, DAT, Dopaminergic neurons, ER, GCase, GSH, GWAS, Glucocerebrosidase, HSPB1, Induced pluripotent stem cell, LRRK2, Leucine rich repeat kinase 2, MAPT, MLK, MOA, OS, PD, PINK1, PTEN induced kinase 1, Parkin, Parkinson's disease, TH, ZFN, alpha synuclein, chaperone mediated autophagy, dopamine, dopamine active transporter, endoplasmic reticulum, genome wide association analysis, glucocerebrosidase, glutathione synthase, hESC, heat shock 27 kDa protein 1, human embryonic stem cell, iPSC, induced pluripotent stem cell, leucine rich repeat kinase 2, microtubule associated protein tau, mixed lineage kinase, monoamine oxidase, oxidative stress, tyrosine hydroxylase, zinc finger nuclease, α-SYN, Cell Differentiation, Dopaminergic Neurons, Glucosylceramidase, Humans, Induced Pluripotent Stem Cells, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, Models, Genetic, Mutation, Parkinson Disease, Protein Kinases, Protein Serine-Threonine Kinases, Ubiquitin-Protein Ligases, alpha-Synuclein