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New Target for Treatment of Parkinsonís Symptoms
- Feb 28 2012
Scientists may have discovered a new approach for the treatment of Parkinson’s disease (PD). According to research published in the January 26 issue of Neuron, a protein called RGS4 could be a potential target for future therapies.
Normally, RGS4 helps regulate movement in a part of the brain called the striatum. Previously, researchers had demonstrated that the loss of dopamine that occurs in Parkinson’s causes a large increase in the amount of RGS4 in the brain. They also showed that this increase in RGS4 directly affected the release of acetylcholine, a neurotransmitter involved in the control of movements. These findings strongly implicated RGS4 in the symptoms of PD.
To investigate the role of RGS4 in Parkinson’s motor symptoms, Talia Lerner, B.S., and Anatol Kreitzer, Ph.D., of the Gladstone Institute for Neurological Disease at the University of California, San Francisco created two groups of mice with dopamine deficiency induced by a toxin, simulating PD – one group with RGS4 in the brain, and one group without it. They first studied the brains from these mice to examine whether RGS4 alters the ability of brain cells to adjust their connections with other neighboring brain cells, a critical process known as plasticity. They then tested the two groups of mice using standard tests of motor function, including the open field test in which mice were released into a circular arena and total movement was measured, and a balance test in which the mice were placed on a balance beam.
- While the mice with RGS4 had impaired plasticity, the mice without RGS4 had normal levels of plasticity.
- Mice lacking RGS4 demonstrated normal levels of movement in the open field test in spite of dopamine deficiency, when measured either by the distance traveled or the amount of time spent motionless.
- Mice with RGS4 were severely impaired and showed much less movement.
- The balance beam test, which tests for motor coordination, revealed that mice with RGS4 had large deficits in coordination and regularly failed to cross the beam. The mice without RGS4 crossed the beam with ease and fell as rarely as normal mice.
What Does it Mean?
Because many of the debilitating symptoms of PD are related to deficits in motor function, the finding that mice without RGS4 – which were treated with toxins that simulate dopamine deficiency – have near-normal motor function signifies a very important discovery. Typically, motor symptoms are treated by attempting to replace the dopamine lost during the progression of PD. While this works well at first, the progression of the disease eventually requires a large amount of dopamine to be taken, causing often-debilitating side effects. This research suggests that reducing the amount of RGS4 in the brain could serve as a parallel course of PD treatment.
Because this study demonstrates that dopamine loss alone is not sufficient to cause motor dysfunction in mice, it shows that PD cannot be completely understood just by looking at the levels and actions of dopamine. Instead, PD symptoms are the result of a web of interactions between different molecules acting in different pathways. While this makes understanding Parkinson’s more complicated, it also means that there may be more avenues to treatment than those that are currently known. If further research in humans confirms the role of RGS4, drugs that reduce its levels may represent one possible therapeutic avenue.
Reference: Lerner, T. N., & Kreitzer, A. C. (2012). RGS4 Is Required for Dopaminergic Control of Striatal LTD and Susceptibility to Parkinsonian Motor Deficits. Neuron, 73(2), 347–359. doi:10.1016/j.neuron.2011.11.015
Source Date: Feb 28 2012