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Proteostasis and Inflammation: New Insights and Therapeutic Strategies in Neurodegeneration
The fast progress in human genetics reveals common molecular mechanisms in aging-related neurodegenerative diseases, such as Alzheimer's disease (AD) and Frontotemporal Dementia (FTD). I will focus the discussion on two converging pathways linking AD and FTD, including innate immunity and proteostasis. In human iPSC and mouse models of disease, our research employs a combination of in vitro and in vivo approaches, such as genomic and proteomic approaches, electrophysiology, and behavioral tests. I will discuss our recent work on identification of key pathways in microglia-mediated neuronal injury and novel mechanisms regulating homeostasis of tau, a key pathogen in AD and FTD. I will also discuss how dysregulated innate immune response contributes to proteostasis malfunction.