Parkinson’s disease (PD) – a neurodegenerative disease that causes loss of motor function – results from interactions between genetic and environmental risk factors that are not fully understood.

Aaron Bowman, Ph.D., and colleagues tested the hypothesis that a genetic predisposition to PD makes neurons more vulnerable to exposure to heavy metals, a known environmental risk factor for PD.

The investigators generated human induced pluripotent stem cells (hiPSCs) from patients with mutations in the PARK2 gene, one of the most common causes of early onset PD, and from controls without mutations or a family history of PD. They found that PARK2 mutant neuroprogenitors – neural cells derived from the hiPSCs – showed increased vulnerability to copper and cadmium cytotoxicity, compared to controls. The cells had a substantial increase in reactive oxygen species and mitochondrial dysfunction after copper exposure.

The findings, reported in the January issue of Neurobiology of Disease, substantiate copper as an environmental risk factor for PD. They also support the potential of patient-specific hiPSCs to define individualized environmental risks.

This research was supported by the Doris Duke Charitable Foundation, a Hazinski-Turner Award, the Peterson Foundation for Parkinson’s, PK Hope is Alive! and the National Institutes of Health (grants GM085354, NS078289, ES000267, NS057666, ES016931).

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