Transformed Stem Cells Provide New Platform to Study Parkinson's Disease

Mouse embryonic stem cells (mESCs) that have been induced to transform into dopamine neurons have been adapted as a platform to study the role of the retinoid X receptor (RXR) in the progression of Parkinson's disease.

Investigators at the Ludwig Institute for Cancer Research (Stockholm, Sweden) had previously shown that certain RXR ligands could protect dopamine neurons from the neurodegenerative effects of Parkinson's disease. In the current study, they established a new in vitro system to better explore the interaction between RXR and the disease.

To this end, the investigators grew cultures of mESCs together with rat primary ventral midbrain (vMB) neurons. Under these conditions the mESCs transformed into dopamine producing neuron-like cells.

Results published in the December 11, 2009, online edition of the journal BMC Neuroscience revealed that the RXR ligand LG100268 (LG268) and the RXR-Nurr1 ligand XCT0139508 (XCT) rescued dopamine neurons from degeneration caused by the Parkinson's disease simulating toxin 6-hydroxy dopamine (6-OHDA) as well as hypoxia. The protective effect was selective for dopamine neurons. Dopamine neurons from rat primary vMB and mESCs behaved similarly, but the mESC-derived cultures contained a much higher fraction of dopamine cells, and thus provided more accessible experimental conditions.

Senior author Dr. Susanna Kjellander, professor of pharmacy at the Ludwig Institute for Cancer Research, said, "Nuclear hormone receptors like RXR and the Nurr1-RXR receptor heterodimer are emerging as interesting factors in Parkinson's research. It is unclear exactly how neurons are damaged in Parkinson's disease, but it is suggested that oxidative damage and energy depletion in the brain are involved. By activating RXR, neurons can be rescued from this degeneration."

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Ludwig Institute for Cancer Research