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J Clin Med. 2015 Mar 30;4(4):548-66. doi: 10.3390/jcm4040548.

Using iPS Cells toward the Understanding of Parkinson's Disease.

Author information

1
Institute for Biomedicine of the University of Barcelona (IBUB), Barcelona Science Park, Barcelona 08028, Spain. rtorrent@gmail.com.
2
Institute for Biomedicine of the University of Barcelona (IBUB), Barcelona Science Park, Barcelona 08028, Spain. fdeangelisrigotti@ibub.pcb.ub.es.
3
Department of Molecular and Translational Medicine, Fibroblast Reprogramming Unit, University of Brescia, Brescia 25123, Italy. patrizia.dellera@med.unibs.it.
4
Department of Molecular and Translational Medicine, Fibroblast Reprogramming Unit, University of Brescia, Brescia 25123, Italy. maurizio.memo@med.unibs.it.
5
Control of Stem Cell Potency Group, Institute for Bioengineering of Catalonia (IBEC), Barcelona 08028, Spain. araya@ibecbarcelona.eu.
6
Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona 08010, Spain. araya@ibecbarcelona.eu.
7
Center for Networked Biomedical Research on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid 28029, Spain. araya@ibecbarcelona.eu.
8
Center of Regenerative Medicine in Barcelona, Dr. Aiguader 88, Barcelona 08003, Spain. araya@ibecbarcelona.eu.
9
Institute for Biomedicine of the University of Barcelona (IBUB), Barcelona Science Park, Barcelona 08028, Spain. aconsiglio@ibub.pcb.ub.es.
10
Department of Molecular and Translational Medicine, Fibroblast Reprogramming Unit, University of Brescia, Brescia 25123, Italy. aconsiglio@ibub.pcb.ub.es.

Abstract

Cellular reprogramming of somatic cells to human pluripotent stem cells (iPSC) represents an efficient tool for in vitro modeling of human brain diseases and provides an innovative opportunity in the identification of new therapeutic drugs. Patient-specific iPSC can be differentiated into disease-relevant cell types, including neurons, carrying the genetic background of the donor and enabling de novo generation of human models of genetically complex disorders. Parkinson's disease (PD) is the second most common age-related progressive neurodegenerative disease, which is mainly characterized by nigrostriatal dopaminergic (DA) neuron degeneration and synaptic dysfunction. Recently, the generation of disease-specific iPSC from patients suffering from PD has unveiled a recapitulation of disease-related cell phenotypes, such as abnormal α-synuclein accumulation and alterations in autophagy machinery. The use of patient-specific iPSC has a remarkable potential to uncover novel insights of the disease pathogenesis, which in turn will open new avenues for clinical intervention. This review explores the current Parkinson's disease iPSC-based models highlighting their role in the discovery of new drugs, as well as discussing the most challenging limitations iPSC-models face today.

KEYWORDS:

Leucine-rich repeat kinase 2 (LRRK2); Parkinson’s disease; dopaminergic neurons; induced pluripotent stem cells

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