Parkinson's disease in a dish - Using stem cells as a molecular tool

被引:58
作者
Badger, J. L. [1 ,2 ]
Cordero-Llana, O. [2 ]
Hartfield, E. M. [2 ,3 ]
Wade-Martins, R. [1 ,2 ,3 ]
机构
[1] Univ Oxford, Dept Physiol Anat & Genet, StemBANCC, Oxford OX1 3QX, England
[2] Univ Oxford, Dept Physiol Anat & Genet, Mol Neurodegenerat Grp, Oxford OX1 3QX, England
[3] Univ Oxford, Dept Physiol Anat & Genet, Oxford Parkinsons Dis Ctr, Oxford OX1 3QX, England
关键词
Alpha synuclein; Dopaminergic neurons; Glucocerebrosidase; Induced pluripotent stem cell; Leucine rich repeat kinase 2; Parkin; Parkinson's disease; PINK1; MIDBRAIN DOPAMINERGIC-NEURONS; ALPHA-SYNUCLEIN; GLUCOCEREBROSIDASE GENE; NEUROTROPHIC FACTOR; STRIATAL DOPAMINE; SUBSTANTIA-NIGRA; MICE LACKING; IPS CELLS; HUMAN ES; MUTATIONS;
D O I
10.1016/j.neuropharm.2013.08.035
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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'. (C) 2013 Elsevier Ltd. All rights reserved.
引用
收藏
页码:88 / 96
页数:9
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