Researchers have revealed that three molecules are responsible for neuron death in Parkinson’s disease, providing a better understanding of how to save the neurons.
The three molecules: the neurotransmitter dopamine, a calcium channel, and a protein called alpha-synuclein act together to kill brain cells.
It’s estimated that 4 million individuals worldwide suffer from Parkinson’s disease. The symptoms of Parkinson’s disease, including uncontrollable tremors and difficulty in moving arms and legs, are caused by the loss of neurons from the substantia nigra region of the brain. Current treatments can alleviate the symptoms of Parkinson’s disease, but they do not prevent or halt the degeneration of nerve cells.
Although researchers had previously suspected dopamine, alpha-synuclein and calcium channels were involved in killing the neurons, recent studies show that it is the combination of all three factors that kills the neurons.
The studies found that neurons die because calcium channels lead to an increase of dopamine inside the cell; excess dopamine then reacts with alpha-synuclein to form inactive complexes; and then the complexes gum up the cell’s ability to dispose of toxic waste that builds up in the cell over time. The waste eventually kills the cell. The neurons will survive if just one of the three factors is missing.
“It may be possible to save neurons and stop Parkinson’s disease by interfering with just one of the three factors,” says study author Eugene Mosharov.
The idea that dopamine contributes to the death of neurons may seem paradoxical, since most Parkinson’s disease patients take L-DOPA to increase the amount of dopamine inside the cells.
The new study shows that it’s the location of the dopamine inside the neurons that determines its toxicity.
Most of dopamine inside the neurons is packaged into compartments that are shipped to the edge of the cell where the dopamine is released. The motor symptoms of Parkinson’s disease arise when the amount of dopamine released by the cells declines. L-DOPA improves symptoms by boosting the amount of dopamine released by the cells. As long as dopamine is confined inside the compartments before it is released, it is safe.
Outside the compartments in the cell’s cytoplasm, dopamine in concert with calcium and alpha-synuclei is toxic.
A better treatment may be to push more dopamine into the compartments where it has no toxic effect on the cell. Not only would it stop cells from dying and the disease from progressing, it would improve the patient’s symptoms at the same time by giving their neurons more dopamine to release.
The researchers are currently working on genetic therapies that could accomplish this feat, but caution that it will be years before any such treatment is ready for clinical trials, if ever.
References:
1. Eugene V. Mosharov,et al. Interplay between Cytosolic Dopamine, Calcium, and ?-Synuclein Causes Selective Death of Substantia Nigra Neurons. Neuron, 62(2) pp. 218 – 229.
