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Discovery puts designer dopamine neurons within reach

Science Daily reports that Parkinson’s disease researchers at the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo have developed a way to ramp up the conversion of skin cells into dopamine neurons. They have identified — and found a way to overcome -a key obstacle to such cellular conversions. At the same time, the researchers say the finding has profound implications for changing the way scientists work with all cells.

The new research, published 0n December 7th in Nature Communications, revolves around their discovery that p53, a transcription factor protein, acts as a gatekeeper protein.

“We found that p53 tries to maintain the status quo in a cell, it guards against changes from one cell type to another,” explained Jian Feng, PhD, senior author and professor in the Department of Physiology and Biophysics in the Jacobs School of Medicine and Biomedical Sciences at UB. “We found that p53 acts as a kind of gatekeeper protein to prevent conversion into another type of cell. Once we lowered the expression of p53, then things got interesting: We were able to reprogram the fibroblasts into neurons much more easily.”

“Our method is faster and much more efficient than previously developed ones,” said Feng. “The best previous method could take two weeks to produce 5 percent dopamine neurons. With ours, we got 60 percent dopamine neurons in ten days.”

The researchers have done multiple experiments to prove that these neurons are functional mid-brain dopaminergic neurons, the type lost in Parkinson’s disease.

The finding enables researchers to generate patient-specific neurons in a dish that could then be transplanted into the brain to repair the faulty neurons. It can also be used to efficiently screen new treatments for Parkinson’s disease.

Journal Reference:

Houbo Jiang, Zhimin Xu, Ping Zhong, Yong Ren, Gaoyang Liang, Haley A. Schilling, Zihua Hu, Yi Zhang, Xiaomin Wang, Shengdi Chen, Zhen Yan, Jian Feng. Cell cycle and p53 gate the direct conversion of human fibroblasts to dopaminergic neurons. Nature Communications, 2015; 6: 10100 DOI: 10.1038/ncomms10100

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