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.
机构:
Univ Oxford, Dept Expt Psychol, Oxford OX1 3QX, England
Univ Oxford, Oxford Parkinsons Dis Ctr, Oxford OX1 3QX, EnglandCardiff Univ, Sch Biosci, Cardiff CF10 3AX, S Glam, Wales
Deacon, Robert M.
;
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Bannerman, David M.
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Bolam, J. Paul
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h-index: 0
机构:
Univ Oxford, Oxford Parkinsons Dis Ctr, Oxford OX1 3TH, England
Univ Oxford, Med Res Council Anat Neuropharmacol Unit, Dept Pharmacol, Oxford OX1 3TH, EnglandCardiff Univ, Sch Biosci, Cardiff CF10 3AX, S Glam, Wales
Bolam, J. Paul
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Chandra, Sreeganga S.
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机构:
Yale Univ, Program Cellular Neurosci Neurodegenerat & Repair, Dept Neurol, Dept Mol Cellular & Dev Biol, New Haven, CT 06536 USACardiff Univ, Sch Biosci, Cardiff CF10 3AX, S Glam, Wales
机构:
Univ British Columbia, Dept Med Neurol, Pacific Parkinsons Res Ctr, Vancouver, BC V6T 2B5, CanadaUniv British Columbia, Dept Med Neurol, Pacific Parkinsons Res Ctr, Vancouver, BC V6T 2B5, Canada
Appel-Cresswell, Silke
;
Vilarino-Guell, Carles
论文数: 0引用数: 0
h-index: 0
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Univ British Columbia, Dept Med Genet, Ctr Appl Neurogenet, Vancouver, BC V6T 2B5, CanadaUniv British Columbia, Dept Med Neurol, Pacific Parkinsons Res Ctr, Vancouver, BC V6T 2B5, Canada
Vilarino-Guell, Carles
;
Encarnacion, Mary
论文数: 0引用数: 0
h-index: 0
机构:
Univ British Columbia, Dept Med Genet, Ctr Appl Neurogenet, Vancouver, BC V6T 2B5, CanadaUniv British Columbia, Dept Med Neurol, Pacific Parkinsons Res Ctr, Vancouver, BC V6T 2B5, Canada
Encarnacion, Mary
;
Sherman, Holly
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Univ British Columbia, Dept Med Genet, Ctr Appl Neurogenet, Vancouver, BC V6T 2B5, CanadaUniv British Columbia, Dept Med Neurol, Pacific Parkinsons Res Ctr, Vancouver, BC V6T 2B5, Canada
Sherman, Holly
;
Yu, Irene
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Univ British Columbia, Dept Med Genet, Ctr Appl Neurogenet, Vancouver, BC V6T 2B5, CanadaUniv British Columbia, Dept Med Neurol, Pacific Parkinsons Res Ctr, Vancouver, BC V6T 2B5, Canada
Yu, Irene
;
Shah, Brinda
论文数: 0引用数: 0
h-index: 0
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Univ British Columbia, Dept Med Genet, Ctr Appl Neurogenet, Vancouver, BC V6T 2B5, CanadaUniv British Columbia, Dept Med Neurol, Pacific Parkinsons Res Ctr, Vancouver, BC V6T 2B5, Canada
Shah, Brinda
;
Weir, David
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Univ British Columbia, Dept Med Neurol, Pacific Parkinsons Res Ctr, Vancouver, BC V6T 2B5, CanadaUniv British Columbia, Dept Med Neurol, Pacific Parkinsons Res Ctr, Vancouver, BC V6T 2B5, Canada
Weir, David
;
Thompson, Christina
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Univ British Columbia, Dept Med Genet, Ctr Appl Neurogenet, Vancouver, BC V6T 2B5, CanadaUniv British Columbia, Dept Med Neurol, Pacific Parkinsons Res Ctr, Vancouver, BC V6T 2B5, Canada
Thompson, Christina
;
Szu-Tu, Chelsea
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h-index: 0
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Univ British Columbia, Dept Med Genet, Ctr Appl Neurogenet, Vancouver, BC V6T 2B5, CanadaUniv British Columbia, Dept Med Neurol, Pacific Parkinsons Res Ctr, Vancouver, BC V6T 2B5, Canada
Szu-Tu, Chelsea
;
Trinh, Joanne
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Univ British Columbia, Dept Med Genet, Ctr Appl Neurogenet, Vancouver, BC V6T 2B5, CanadaUniv British Columbia, Dept Med Neurol, Pacific Parkinsons Res Ctr, Vancouver, BC V6T 2B5, Canada
Trinh, Joanne
;
Aasly, Jan O.
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h-index: 0
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St Olavs Hosp, Dept Neurol, Trondheim, NorwayUniv British Columbia, Dept Med Neurol, Pacific Parkinsons Res Ctr, Vancouver, BC V6T 2B5, Canada
Aasly, Jan O.
;
Rajput, Alex
论文数: 0引用数: 0
h-index: 0
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Univ Saskatchewan, Div Neurol, Saskatoon, SK, Canada
Saskatoon Hlth Reg, Saskatoon, SK, CanadaUniv British Columbia, Dept Med Neurol, Pacific Parkinsons Res Ctr, Vancouver, BC V6T 2B5, Canada
Rajput, Alex
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Rajput, Ali H.
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Stoessl, A. Jon
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h-index: 0
机构:
Univ British Columbia, Dept Med Neurol, Pacific Parkinsons Res Ctr, Vancouver, BC V6T 2B5, CanadaUniv British Columbia, Dept Med Neurol, Pacific Parkinsons Res Ctr, Vancouver, BC V6T 2B5, Canada
Stoessl, A. Jon
;
Farrer, Matthew J.
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h-index: 0
机构:
Univ British Columbia, Dept Med Neurol, Pacific Parkinsons Res Ctr, Vancouver, BC V6T 2B5, Canada
Univ British Columbia, Dept Med Genet, Ctr Appl Neurogenet, Vancouver, BC V6T 2B5, CanadaUniv British Columbia, Dept Med Neurol, Pacific Parkinsons Res Ctr, Vancouver, BC V6T 2B5, Canada
机构:
Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA
Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA
Harvard Univ, Sch Med, Boston, MA 02114 USAFree Univ Berlin, Inst Chem & Biochem, D-14195 Berlin, Germany
机构:
Univ Oxford, Dept Expt Psychol, Oxford OX1 3QX, England
Univ Oxford, Oxford Parkinsons Dis Ctr, Oxford OX1 3QX, EnglandCardiff Univ, Sch Biosci, Cardiff CF10 3AX, S Glam, Wales
Deacon, Robert M.
;
论文数: 引用数:
h-index:
机构:
Bannerman, David M.
;
Bolam, J. Paul
论文数: 0引用数: 0
h-index: 0
机构:
Univ Oxford, Oxford Parkinsons Dis Ctr, Oxford OX1 3TH, England
Univ Oxford, Med Res Council Anat Neuropharmacol Unit, Dept Pharmacol, Oxford OX1 3TH, EnglandCardiff Univ, Sch Biosci, Cardiff CF10 3AX, S Glam, Wales
Bolam, J. Paul
;
Chandra, Sreeganga S.
论文数: 0引用数: 0
h-index: 0
机构:
Yale Univ, Program Cellular Neurosci Neurodegenerat & Repair, Dept Neurol, Dept Mol Cellular & Dev Biol, New Haven, CT 06536 USACardiff Univ, Sch Biosci, Cardiff CF10 3AX, S Glam, Wales
机构:
Univ British Columbia, Dept Med Neurol, Pacific Parkinsons Res Ctr, Vancouver, BC V6T 2B5, CanadaUniv British Columbia, Dept Med Neurol, Pacific Parkinsons Res Ctr, Vancouver, BC V6T 2B5, Canada
Appel-Cresswell, Silke
;
Vilarino-Guell, Carles
论文数: 0引用数: 0
h-index: 0
机构:
Univ British Columbia, Dept Med Genet, Ctr Appl Neurogenet, Vancouver, BC V6T 2B5, CanadaUniv British Columbia, Dept Med Neurol, Pacific Parkinsons Res Ctr, Vancouver, BC V6T 2B5, Canada
Vilarino-Guell, Carles
;
Encarnacion, Mary
论文数: 0引用数: 0
h-index: 0
机构:
Univ British Columbia, Dept Med Genet, Ctr Appl Neurogenet, Vancouver, BC V6T 2B5, CanadaUniv British Columbia, Dept Med Neurol, Pacific Parkinsons Res Ctr, Vancouver, BC V6T 2B5, Canada
Encarnacion, Mary
;
Sherman, Holly
论文数: 0引用数: 0
h-index: 0
机构:
Univ British Columbia, Dept Med Genet, Ctr Appl Neurogenet, Vancouver, BC V6T 2B5, CanadaUniv British Columbia, Dept Med Neurol, Pacific Parkinsons Res Ctr, Vancouver, BC V6T 2B5, Canada
Sherman, Holly
;
Yu, Irene
论文数: 0引用数: 0
h-index: 0
机构:
Univ British Columbia, Dept Med Genet, Ctr Appl Neurogenet, Vancouver, BC V6T 2B5, CanadaUniv British Columbia, Dept Med Neurol, Pacific Parkinsons Res Ctr, Vancouver, BC V6T 2B5, Canada
Yu, Irene
;
Shah, Brinda
论文数: 0引用数: 0
h-index: 0
机构:
Univ British Columbia, Dept Med Genet, Ctr Appl Neurogenet, Vancouver, BC V6T 2B5, CanadaUniv British Columbia, Dept Med Neurol, Pacific Parkinsons Res Ctr, Vancouver, BC V6T 2B5, Canada
Shah, Brinda
;
Weir, David
论文数: 0引用数: 0
h-index: 0
机构:
Univ British Columbia, Dept Med Neurol, Pacific Parkinsons Res Ctr, Vancouver, BC V6T 2B5, CanadaUniv British Columbia, Dept Med Neurol, Pacific Parkinsons Res Ctr, Vancouver, BC V6T 2B5, Canada
Weir, David
;
Thompson, Christina
论文数: 0引用数: 0
h-index: 0
机构:
Univ British Columbia, Dept Med Genet, Ctr Appl Neurogenet, Vancouver, BC V6T 2B5, CanadaUniv British Columbia, Dept Med Neurol, Pacific Parkinsons Res Ctr, Vancouver, BC V6T 2B5, Canada
Thompson, Christina
;
Szu-Tu, Chelsea
论文数: 0引用数: 0
h-index: 0
机构:
Univ British Columbia, Dept Med Genet, Ctr Appl Neurogenet, Vancouver, BC V6T 2B5, CanadaUniv British Columbia, Dept Med Neurol, Pacific Parkinsons Res Ctr, Vancouver, BC V6T 2B5, Canada
Szu-Tu, Chelsea
;
Trinh, Joanne
论文数: 0引用数: 0
h-index: 0
机构:
Univ British Columbia, Dept Med Genet, Ctr Appl Neurogenet, Vancouver, BC V6T 2B5, CanadaUniv British Columbia, Dept Med Neurol, Pacific Parkinsons Res Ctr, Vancouver, BC V6T 2B5, Canada
Trinh, Joanne
;
Aasly, Jan O.
论文数: 0引用数: 0
h-index: 0
机构:
St Olavs Hosp, Dept Neurol, Trondheim, NorwayUniv British Columbia, Dept Med Neurol, Pacific Parkinsons Res Ctr, Vancouver, BC V6T 2B5, Canada
Aasly, Jan O.
;
Rajput, Alex
论文数: 0引用数: 0
h-index: 0
机构:
Univ Saskatchewan, Div Neurol, Saskatoon, SK, Canada
Saskatoon Hlth Reg, Saskatoon, SK, CanadaUniv British Columbia, Dept Med Neurol, Pacific Parkinsons Res Ctr, Vancouver, BC V6T 2B5, Canada
Rajput, Alex
;
论文数: 引用数:
h-index:
机构:
Rajput, Ali H.
;
Stoessl, A. Jon
论文数: 0引用数: 0
h-index: 0
机构:
Univ British Columbia, Dept Med Neurol, Pacific Parkinsons Res Ctr, Vancouver, BC V6T 2B5, CanadaUniv British Columbia, Dept Med Neurol, Pacific Parkinsons Res Ctr, Vancouver, BC V6T 2B5, Canada
Stoessl, A. Jon
;
Farrer, Matthew J.
论文数: 0引用数: 0
h-index: 0
机构:
Univ British Columbia, Dept Med Neurol, Pacific Parkinsons Res Ctr, Vancouver, BC V6T 2B5, Canada
Univ British Columbia, Dept Med Genet, Ctr Appl Neurogenet, Vancouver, BC V6T 2B5, CanadaUniv British Columbia, Dept Med Neurol, Pacific Parkinsons Res Ctr, Vancouver, BC V6T 2B5, Canada
机构:
Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA
Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA
Harvard Univ, Sch Med, Boston, MA 02114 USAFree Univ Berlin, Inst Chem & Biochem, D-14195 Berlin, Germany