Karina Vargas Receives Grant to Study Synaptic Dysfunction in Parkinson’s Disease

Modern medicine has provided an increase in life expectancy, but along with this gain has come an increase in cases of neurodegenerative disease. Parkinson’s disease, a motor disorder characterized by stiffness, tremors and slowness of movement, is the second most common neurodegenerative disease. Its symptoms are caused by death of dopaminergic neurons in the brain. Parkinson’s disease has no cure, can only be detected in late stages, and has only palliative treatment available.

Much research has focused on finding the origin of Parkinson’s disease, yet scientists are unfortunately still far from it. Nevertheless, the scientific community has no doubt that the protein a-synuclein is a key factor in the pathogenesis of Parkinson’s disease.

Parkinson’s is a disease of the synapse, the communication junction between nerve cells. Synaptic dysfunction is correlated with cognitive impairment in several neurodegenerative diseases, including Parkinson’s. Thus, there is an imperative need to fix synapses in these patients.

Communication between neurons occurs when an electrical impulse stimulates a neuron to release a neurotransmitter, which activates the next neuron. A process called clathrin mediated endocytosis helps maintain the neurons’ release of neurotransmitter and allows neurons to be ready to activate every time a nerve impulse arrives.

a-Synuclein is located in the presynapse, the part of the neuron that contains the synaptic vesicles loaded with neurotransmitter. It is not completely understood how this protein works in the synapse. The completion of that research can illuminate the origin of Parkinson’s disease and suggest effective ways to treat it.

To pursue this, MBL Research Scientist Karina Vargas recently received a grant from the National Institutes of Health called "Roles for alpha-Synuclein in Clathrin-Mediated Synaptic Vesicle Recycling". Vargas will observe a-synuclein in the synapses of lampreys and mice. “The sea lamprey is a wonderful model for synaptic studies. The particularly large size of its synapse combined with MBL’s state-of-the-art microscopy makes the observations clear,” she says.  In the lamprey synapse, Vargas will investigate where a-synuclein, clathrin and the synaptic vesicle are. Using the mouse model, Vargas will study different proteins from clathrin-mediated endocytosis that are working with a-synuclein. The ultimate goal of the project is to discover which proteins are a-synuclein partners and how they work together to affect the endocytosis of synaptic vesicles and, thus, neurotransmission.