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Neurobiology Virtual Seminar Series

Apr 21

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Tuesday, April 21, 2020 - 12:00pm to 1:00pm

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Andrew West

Andrew West will present "Genetic and neurobiologic ties to endosome dysfunction in neurodegeneration" on Zoom. Email for connection details. Abstract: Parkinson's disease and related Lewy body diseases, including dementia with Lewy bodies, represent common causes of Alzheimer's disease related dementias. Although therapies that might slow or halt disease have not been found, recent discoveries from human genetics, post-mortem tissue studies, and disease models have zeroed in on a few genes hypothesized to control disease susceptibility and progression. While the aggregation of a-synuclein into inclusions pathologically defines these diseases, tens of thousands of Americans harbor genetic LRRK2 missense mutations that cause PD and hyperactivate LRRK2. Recently, we observed a dual-induction phenomenon in LRRK2 regulating a-synuclein aggregation in neurons, as well as inducible LRRK2 expression in pro-inflammatory myeloid cells responding to a-synuclein aggregation. Our attention now moves to endosomes and lysosomes in neurons and macrophages, where we find LRRK2 interacting in-complex with other proteins independently linked to neurodegeneration that include Rab10, VPS35, and Rab29. We continue to pursue testing a hypothesis whereby disrupted vesicle traffic and degradation in the cytoplasm leads to both a-synuclein aggregation in vulnerable neurons and immunological responses that result in neurodegeneration.