Neurobiology of Parkinson's Disease

Dr. McLean's laboratory focuses on understanding the cellular and molecular mechanisms underlying neuroregeneration in Parkinson's disease, dementia with Lewy bodies and related disorders. Parkinson's disease is the most common movement disorder, affecting approximately 1 percent of the general population in the United States. It is characterized clinically by the appearance of tremor, slowed movement and speech (bradykinesia), muscle rigidity, and postural instability.

Pathologically, the disease presents as a loss of neurons in the substantia nigra, leading to a loss in the neurotransmitter dopamine as well as the presence of protein accumulations inside neurons called Lewy bodies in affected brain regions. Sporadic Parkinson's disease accounts for 90 to 95 percent of cases and is thought to be due to a combination of environmental and complicated genetic factors. The remaining 5 to 10 percent are due to specific gene mutations in one of multiple genes associated with the disease. The first gene to be genetically linked to Parkinson's disease is the alpha-synuclein gene, which encodes a protein called alpha-synuclein. Alpha-synuclein is a small, presynaptic protein that misfolds and accumulates in Lewy bodies in the brain.

Dr. McLean and her colleagues develop and use cell-based and animal models to study the role of alpha-synuclein in Parkinson's disease and the related Lewy body dementia. Research projects focus on understanding the improper folding and aggregation of alpha-synuclein that occurs in the disease process.

The lab uses cell and animal models as powerful tools to study what causes alpha-synuclein to aggregate and accumulate in cells, as well as to explore ways to remove the abnormal protein and protect the cells. Ultimately the goal is to translate research findings into new therapies for the many patients who suffer from these devastating diseases.