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King's College London
Institute of Pharmaceutical Science
PhD student at KCL
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University of Latvia
Department of Pharmacology
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Center for Translational Research in Neurodegenerative disease
Neuroscience
KU Leuven - VIB
KU Leuven - VIB Center for Brain and Disease Research
As a PhD student, I was interested in how nerve endings sustain activity. Local pathways at nerve endings must exist to minimize energy consumption of the neuron. I analyzed the role of Skywalker and we showed that Skywalker defines a novel pathway that regulates protein quality at nerve endings (Uytterhoeven, Cell 2011, Fernandes, Journal of Cell Biology 2014). More recent work that was initiated under my impulse, implicates the Skywalker process in epilepsy (Fischer, Nature Structural and Molecular Biology 2016). During my Postdoc, I uncovered a second protein quality control pathway at nerve endings (Uytterhoeven, Neuron 2015). We not only show that it regulates the turnover of specific proteins at nerve endings, but we also show a novel function for the heat shock protein, Hsc70-4 regulating this pathway. Today, I study the molecular mechanism of Tau and implicate the Hsc70-4 mediated turn over system in Tau related defects at the presynapse. Our work shows that we can genetically restore neuronal activity/health and rescue memory defects in Tau mutant animal models (fly and mouse) by modulating 1) Tau degradation or 2) Tau-presynaptic vesicle interactions (Largo-Barrientos, 2021) at nerve endings. Hence, I focus on unraveling presynaptic molecular defects in dementia.