Pathological Mechanisms of Parkinsonism
Dr. Nick McFarland and his team focus on understanding the pathological mechanisms of Parkinson disease and related disorders (atypical parkinsonisms or Parkinson-plus disorders) and in particular the role of alpha-synuclein in cell toxicity and neurodegeneration. A major hallmark of neurodegenerative disorders, including Parkinson disease, is abnormal protein aggregation and deposition. In Parkinson disease and related disorders, intracellular inclusions called Lewy bodies are found. A principal component of these Lewy bodies is alpha-synuclein. Abnormal folding, aggregation, and deposition of alpha-synuclein are believed to be central to the development of neuronal dysfunction and degeneration.
A primary goal of this parkinsonism research is to elucidate the mechanisms of alpha-synuclein and related proteins that cause toxicity and to characterize molecular mediators that may enhance or rescue toxicity. Work involves use of cellular, neuronal, and preclinical animal models that employ genetic overexpression of alpha-synuclein and allow for testing of various genes, molecules, and compounds that may modify toxicity and have the potential for novel therapeutics.
The lab is located in the Center for Translational Research in Neurodegenerative Disease, directed by Dr. Todd Golde. The Center is a highly collaborative group focused on understanding and translating findings from basic research on neurodegenerative diseases, such as Parkinson, Alzheimer’s, and Huntington’s disease, into novel therapies. We work closely with a number of departments, including Neuroscience and Neurology, the McKnight Brain Institute, and the Center for Aging among others here at the University of Florida.
Research areas and initiatives
- Understanding the role of cellular (neuronal) trafficking proteins and how they are affected by abnormal protein accumulation, deposition in Parkinson disease and related disorders
- Testing of novel compounds, HDAC and sirtuin inhibitors, in preclinical models of Parkinsonism
- Examining the role of urate, or uric acid, in Parkinson disease – collaboration with MGH
- Developing a multidisciplinary group and approach to help those with atypical parkinsonisms, such as Progressive Supranuclear Palsy. Research includes collaborations with Dr. Chris Hass for gait and motor analysis, neuropsychiatry, and others to understand specific cognitive and mood problems in this patient population.