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

• Analysis of studies using DA neurons from PD patient-derived iPSCs to model PD in vitro.
• We focus on the results shown in 5 key PD-associated genes: LRRK2, GBA1, PINK1, PARK2 and SNCA.
• Multiple affected cell systems might converge onto a common pathway that mediates DA neuronal death.

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’.