Newly Identified Protein May Help Damaged Dopamine Neurons Recover in Parkinson’s Disease

Scientists supported by the Parkinson’s Disease Foundation (PDF) have shown that in mice, a newly identified protein can help damaged dopamine neurons to recover and resume their work, which could one day provide a new strategy for treating Parkinson’s disease (PD). The results appear in the August 15, 2012 issue of The Journal of Neuroscience.

Scientists are beginning to understand that substances called trophic factors help adult brain cells (also known as neurons) to stay alive. But exactly how trophic factors and the proteins they activate are able to help neurons, like the ones lost in Parkinson’s, is not well understood.

In the new study, researchers led by Robert E. Burke, M.D., at the PDF Research Center at Columbia University Medical Center, investigated the impact of a specific trophic protein – known as SGK or serum-and glucocorticoid-inducible kinase – on dopamine neurons in the brains of mice.

Dr. Burke and his colleagues worked with mice, engineering their dopamine neurons to make very high levels of SGK. In some mice, the scientists engineered the high levels of SGK first and then treated mice with a toxin that kills dopamine neurons (causing Parkinsonian symptoms), to see whether SGK prevented dopamine neurons from dying. In others, scientists first treated mice with the toxin and then engineered the production of high levels of SGK, to find out whether SGK could restore the function of dying dopamine neurons

Results

The study discovered several effects of SGK:

• SGK was able to protect dopamine neurons from the toxin.
• SGK was able to restore the function of some dopamine neurons and keep them from dying.
• SGK had two important effects on dopamine neurons: it increased the size of the cell and restored their connections to other neurons, allowing them to function again.

What Does It Mean?

This new research shows that SGK not only helps dopamine neurons survive but also helps them maintain healthy axons, and can even restore the function of damaged axons.

Most current Parkinson research has focused on trying to prevent the death of dopamine neurons lost during Parkinson’s disease. However, this research has not always accounted for axons, the part of neurons that allow them to communicate with each other.


In previous research, Dr. Burke recognized the importance of saving and restoring axons and neurons (see his work here). He recognized that saving cell body of the neuron without saving its axons does no good.

His lab’s approach in this study, offers a new approach to developing neurorestorative therapies for PD. These types of therapies are still in the distant future, because there is still much yet to learn about how proteins like SGK work. But this study offers a promising approach for scientists to pursue.

Research in the Burke laboratory is supported by the Parkinson’s Disease Foundation as part of our long-standing commitment to discovering the basic science underlying the development and treatment of PD.
Reference: Chen, X., Tagliaferro, P., Kareva, T., Yarygina, O., Kholodilov, N., & Burke, R. E. (2012). Neurotrophic Effects of Serum- and Glucocorticoid-Inducible Kinase on Adult Murine Mesencephalic Dopamine Neurons. The Journal of Neuroscience, 32(33), 11299–11308. doi:10.1523/JNEUROSCI.5910-11.2012