title: Understanding Parkinson's Disease through the Use of Cell Reprogramming.
abstract: Recent progress in the field of somatic cell reprogramming offers exciting new possibilities for the study and treatment of Parkinson's disease (PD). Reprogramming technology offers the ability to untangle the diverse contributing risk factors for PD, such as ageing, genetics and environmental toxins. In order to gain novel insights into such a complex disease, cell-based models of PD should represent, as closely as possible, aged human dopaminergic neurons of the substantia nigra. However, the generation of high yields of functionally mature, authentic ventral midbrain dopamine (vmDA) neurons has not been easy to achieve. Furthermore, ensuring cells represent aged rather than embryonic neurons has presented a significant challenge. To date, induced pluripotent stem (iPS) cells have received much attention for modelling PD. Nonetheless, direct reprogramming strategies (either to a neuronal or neural stem/progenitor fate) represent a valid alternative that are yet to be extensively explored. Direct reprogramming is faster and more efficient than iPS cell reprogramming, and appears to conserve age-related markers. At present, however, protocols aiming to derive authentic, mature vmDA neurons by direct reprogramming of adult human somatic cells are sorely lacking. This review will discuss the strategies that have been employed to generate vmDA neurons and their potential for the study and treatment of PD.
authors.affiliation: Department of Pharmacology and Clinical Pharmacology, Centre for Brain Research, School of Medical Science, FMHS, University of Auckland, Auckland, 1023, New Zealand.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Playne
authors.affiliation: Department of Pharmacology and Clinical Pharmacology, Centre for Brain Research, School of Medical Science, FMHS, University of Auckland, Auckland, 1023, New Zealand. b.connor@auckland.ac.nz.
authors.forename: Bronwen
authors.identifier: 0000-0001-6828-4175
authors.initials: B
authors.lastname: Connor
mesh_terms: D002454:Cell Differentiation / Q000235:genetics; D065150:Cellular Reprogramming; D059290:Dopaminergic Neurons / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation; D008959:Models, Neurological; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D010300:Parkinson Disease / Q000235:genetics / Q000628:therapy*; D033581:Stem Cell Transplantation; D013378:Substantia Nigra / Q000166:cytology / Q000378:metabolism
keywords: Direct reprogramming; Disease modelling; Dopamine neurons; Induced neural stem cells; Induced neurons; Induced pluripotent stem cells; Parkinson’s disease; Reprogramming