A New Hope for Treatment of Parkinson Disease
Parkinson disease is a central nervous system disorder. In this disease treatment can help but cannot be cured. In the previous studies, a protein Nurr1 has been identified as a potential target for the treatment of Parkinson’s disease but due to its normal form, it is unusable because it cannot penetrate cells.
What is Nurr1?
Nurr1 is a transcription factor which binds to DNA and controls many properties in cells that produce the neurotransmitter dopamine and that are affected by Parkinson’s disease. Dopamine withdrawal in certain brain regions is responsible for the slowness of movement that is associated with the disease.
A new study led by the team from Ruhr-Universität Bochum and the US-American National Institutes of Health (NIH) Researchers have modified the protein Nurr1 so that it can enter cells from the outside.
During their study, the researchers delivered Nurr1 protein into the cell using bacterial import signal. The researchers also demonstrated that the modified protein may have a positive effect on the survival of nerve cells producing dopamine.
During this study the main aim of the researcher was to make Nurr1 protein to penetrate into the cell as nurr1 protein lack this property hence They found what they were looking for in bacteria and attached a fragment of a protein derived from Bacillus anthracis to Nurr1.
In the bacterium, that protein ensures that the pathogen can infiltrate animal cells. “The fragment of a bacterial protein that we used does not trigger diseases; it merely contains the command to transport something into the cell,” explains Rolf Heumann. Once the protein was modified and has been taken up by the cell, the bacterial protein building block is detached, and the Nurr1 protein can reach its target genes by using the cell’s endogenous nuclear import machinery.
The researchers measured the effect of functional delivery of Nurr1 by monitoring the production of the enzyme tyrosine hydroxylase. That enzyme is a precursor in dopamine synthesis – a process that is disrupted in Parkinson’s patients. Cultured cells that were treated with modified Nurr1 produced more tyrosine hydroxylase than untreated cells. At the same time, they produced less Nur77 protein, which is involved in the regulation of programmed cell death.
Moreover, the researchers tested the effect of modified Nurr1 on cultured cells that they treated with the neurotoxin 6-hydroxydopamine. It causes the dopamine-producing cells to die and is thus a model for Parkinson’s disease. Nurr1 inhibited the neurotoxin-induced degeneration of cells.
Future of the Study
“We hope we can thus pave the way for new Parkinson’s therapy,” concludes Sebastian Neumann. “Still, our Nurr1 fusion protein can merely kick off the development of a new approach. Many steps still remain to be taken in order to clarify if the modified protein specifically reaches the right cells in the brain and how it could be applied.”