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Malu Tansey, PhD
Title: The Role of LRRK2 in Immune and Inflammatory Mechanisms in the Gut-Brain Axis
Date: Thursday, February 14th, 2019
Location: Herklotz Conference Center, Center for Neurobiology of Learning and Memory
Abstract: Links between Parkinson’s disease and the gastrointestinal system have become increasingly common. Mutations in the gene encoding Leucine-Rich Repeat Kinase 2 (LRRK2) are known as the greatest genetic contributor to Parkinson’s disease (PD), but may account for as much as 2% of sporadic PD, and increased risk for Crohn’s disease. G2019S, the most common LRRK2-inherited PD mutation, results in increased kinase activity and is weakly associated with risk for Crohn’s disease. The LRRK2 N2081D SNP is associated with a two-fold higher risk for Crohn’s disease and results in a similar gain-of-function increase in kinase activity as G2019S. We have been investigating the role of LRRK2 in immune cells and in the gut-brain axis within the context of PD pathogenesis.
Published studies from our lab revealed that human peripheral blood immune cells express detectable LRRK2 protein and individuals with sporadic PD have increased levels of total LRRK2 protein that correlates with heightened inflammatory responses. To investigate the functional significance of these findings, we used BAC transgenic mice overexpressing wildtype or G2019S mouse LRRK2 and investigated their peripheral immune cell profiles as a function of age and in response to various immunological challenges and their ability to recover from acute DSS-induced colitis as well as the effects of these peripheral inflammatory insults on the brain. Completion of these studies will advance our understanding of the role of LRRK2 in regulating immune and inflammatory responses in peripheral organs, including the gut, that have the potential to impact brain inflammation, neuronal function, and vulnerability to age-related neurodegenerative diseases like PD.