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Parkinson's disease (PD) is an age-related neurodegenerative disorder with no known cure. In order to better understand the pathological mechanisms which lead to neuronal cell death and to accelerate the process of drug discovery, a reliable in vitro model is required. Unfortunately, research into PD and neurodegeneration in general has long suffered from a lack of adequate in vitro models, mainly due to the inaccessibility of live neurons from vulnerable areas of the human brain. Recent reprogramming technologies have recently made it possible to reliably derive human induced pluripotent stem cells (iPSCs) from patients and healthy subjects to generate specific, difficult to obtain, cellular sub-types. These iPSC-derived cells can be employed to model disease to better understand pathological mechanisms and underlying cellular vulnerability. Therefore, in this chapter, we will discuss the techniques involved in the reprogramming of somatic cells into iPSCs, the evolution of iPSC differentiation methods and their application in neurodegenerative disease modeling.

Original publication

DOI

10.1016/bs.pbr.2019.11.002

Type

Chapter

Publication Date

2020

Volume

252

Pages

3 - 25

Keywords

Dopaminergic neurons, GBA, LRRK2, PINK1, Parkin, Parkinson's disease, Reprogramming, SNCA, iPSC, α-Synuclein