Designer dopamine neurons to treat Parkinson's

In a first, a team involved in Parkinson's disease research at the University at Buffalo (UB) has developed a way to ramp up the conversion of skin cells into dopamine neurons which are normally hidden in the brain.

They have identified - and found a way to overcome - a key obstacle to such cellular conversions. At the same time, the finding has profound implications for changing the way scientists work with all cells.

The new research, published in the journal 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, professor in the Jacobs School of Medicine and Biomedical Sciences at UB.

The team also 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 reprogramme the fibroblasts into neurons much more easily," Feng said.

This is a generic way to change cells from one type to another. "It proves that we can treat the cell as a software system, when we remove the barriers to change," Feng added.

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.