My laboratory is working on understanding both the root causes of Parkinson disease (PD) as well as the origin of the disabling symptoms that appear after long term treatment of the disease. The lab has a strong translational orientation – our goal is to accelerate the delivery of new therapies for Parkinson disease to the patients who desperately need them. A primary focus of the laboratory is understanding the role of the protein alpha-synuclein in PD pathophysiology, and searching for novel approaches for protecting the brain from the effects of excess alpha-synuclein. We use a variety of cellular and rodent models, and are exploring the effects of several chaperone molecules, including those derived from open-ended screens in simple non-mammalian systems. A related interest is the role of neuroinflammation in PD. In human PD, there is a marked brain inflammatory response. Recent work in the Standaert lab using mouse models has led to the idea that this inflammation may be triggered directly by the presence of excess alpha-synuclein. The response involves both microglia as well as the adaptive immune system, and both components may be targets of therapies to prevent or retard the disease. We are also exploring the effect of levodopa on brain function in PD. Levodopa remains the most effective existing treatment, but long-term therapy leads to many unwanted side effects (“wearing off” and “dyskinesia”). The Standaert lab has shown that many of the effects result from abnormal synaptic plasticity in the basal ganglia, and mislocalization of glutamate receptor systems. Recently, we found that the mechanisms responsible for the maintenance of this aberrant plasticity are likely the result of levodopa-induced epigenetic modifications.
