Induced pluripotent stem cells: a tool for modeling Parkinson's disease

Abstract

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder. Among its pathologies, progressive loss of dopaminergic (DA) neurons in the substantia nigra is characteristic and contributes to many of the most severe symptoms of PD. Recent advances in induced pluripotent stem cell (iPSC) technology have made it possible to generate patient-derived DA neuronal cell culture and organoid models of PD. These models have contributed to understanding disease mechanisms and the identification of novel targets and therapeutic candidates. Still needed are better ways to model the age-related aspects of PD, as well as a deeper understanding of the interactions among disease-modifying genes and between genetic and environmental contributions to the etiology and progression of PD.

Keywords: GBA; LRRK2; Pink1/Parkin; VPS35; iPSC; organoids; sporadic PD; α-synuclein.

Figure 1.. Schematic representation of the workflow for using iPSC’s for modelling Parkinson’s disease.

Cells from PD patients are isolated by biopsy, which are then reprogrammed to iPSC. These can be differentiated into dopaminergic neurons which can be used for phenotyping assays, drug screening, and in vivo transplantation in animal models to understand the mechanism underlying PD