Objective: To study the molecular mechanism of G2385R mutation of LRRK2 gene in PD developing, dopaminergic neurons are derived from patient specific induced pluripotent stem cells.

Background: The LRRK2 gene has been associated with both familial and sporadic forms of Parkinson’s disease (PD). Our previous study has shown that the G2385R variant is associated with a higher risk of developing PD in certain Asian populations. But the roles of G2385R playing in the PD pathogenic mechanism is still unknown.

Methods: 5 PD patients with G2385R LRRK2 mutation are recruited. Induced pluripotent stem cells are derived using sendai virus mediated reprogramming with patient peripheral blood cells. Dopaminergic neurons are induced from induced pluripotent stem cells using directed differentiation and characterized.

Results: Patient specific Induced pluripotent stem cells are successfully derived, and expressed pluripotent stem cell markers Oct4, SSEA4, TRA160 and TRA181 at mRNA and protein levels. Dopaminergic neurons are derived from iPS cells using directed differentiaton, and has shown positive staining for Tuj1 and tyrosine hydroxylase. Compared to control group, the patient dopaminergic neurons displayed less dopamine secretion, abnormal mitochondrial ultrastructure and up-regulation of cell death genes.

Conclusions: G2385R patient specific induced pluripotent stem cells and Dopaminergic neurons are derived; the dopaminergic neurons displayed typical PD phenotype in vitro, and provide a valuable cellular model for studying PD mechanism and screening novel drugs.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/generation-of-dopaminergic-neurons-for-studying-parkinsons-disease-using-patient-blood-cells/