SUMMARY
Research in the Neurobiology of Parkinson's Disease Laboratory of Pam J. McLean, Ph.D., focuses on understanding the cellular and molecular mechanisms underlying neurodegeneration in Parkinson's disease, dementia with Lewy bodies and related neurodegenerative conditions. In particular, her research group studies the role of alpha-synuclein, a protein that misfolds and aggregates in the brain regions that are critically involved in these diseases.
Dr. McLean's lab has developed many cell-based models to facilitate studies of alpha-synuclein. In these models, researchers in Dr. McLean's lab can induce the improper folding and aggregation of the alpha-synuclein protein to mimic the disease process. The lab uses these powerful models to study the pathways involved in alpha-synuclein aggregation and toxicity in cells, as well as to explore ways to remove the abnormal protein and protect cells.
In addition to developing cell-based models, Dr. McLean's lab uses animal models and advanced microscopy imaging techniques to study alpha-synuclein misfolding.
Dr. McLean is part of a team of internationally recognized researchers and clinicians with specialty training in Parkinson's disease and movement disorders supported by the American Parkinson Disease Association. Mayo Clinic has been designated an American Parkinson Disease Center for Advanced Research.
Focus areas
- Alpha-synuclein propagation in disease. Although alpha-synuclein has traditionally been thought to exert its detrimental effects inside cells, it is now known that alpha-synuclein can be released from cells and transmitted to neighboring cells. These findings have precipitated new hypotheses that alpha-synuclein propagation from cell to cell may be responsible for the progression of Parkinson's disease and Lewy body disease to different areas of the brain. Dr. McLean's lab is focusing research projects in this exciting area.
- Biomarker discovery. The McLean lab is working to develop early, accessible biomarkers for Lewy body disease. In particular, there is a need for biomarkers that can distinguish dementia with Lewy bodies from Alzheimer's disease when symptoms first appear. The McLean lab is focusing discovery efforts on small extracellular vesicles found in blood that can carry signals from the brain as a way to differentiate these diseases.
- Copathologies in neurodegenerative disease. Neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease are often neuropathologically classified by the accumulation of a specific protein in vulnerable brain regions. However, most neurodegenerative diseases have more-complex neuropathological classifications due to the presence of multiple disease-related pathologies. The McLean lab is investigating the role of comorbid pathologies in neurodegenerative disease.
- Developing novel therapeutics. The McLean lab is working on several projects that focus on developing therapies and translating research findings to benefit patients. Current projects focus on developing a gene therapy approach to target alpha-synuclein and reduce protein levels, developing small molecules that can modulate alpha-synuclein expression, and performing drug screens to identify new molecules for therapeutic development.
Significance to patient care
The goal of Dr. McLean's lab is to uncover the biological basis for brain diseases such as Parkinson's disease and dementia with Lewy bodies. With this knowledge, the lab hopes to create new treatments for these diseases.
The McLean lab puts the needs of the patient first. The lab is committed to finding treatments and a cure for brain diseases that involve the protein alpha-synuclein.