Associate Professor, Laboratory of Transcriptional Neurobiology Department of Cellular, Computational and Integrative Biology – CIBIO University of Trento, ITALY
Thursday, 19 January 2023 | 12:00 noon – ICGEB Trieste, ITALY
An altered extracellular vesicle protein cargo drives the (mis)communication between astrocytes and neurons in Amyotrophic Lateral Sclerosis and Frontotemporal dementia
Host: E. Buratti
Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease characterized by protein inclusions enriched in a protein called TDP-43. Among several factors, the progression of this disease could be mediated by altered intercellular communication between neurons and glial cells. One of the possible ways in which the cell- to-cell communication occurs is through extracellular vesicles (EVs) that transport proteins, lipids and nucleotides from one cell to the other. Our unpublished data suggest that a premature process of aging in glia changes the EVs protein and RNA content, inducing toxicity in receiving neurons. By investigating the timing and amount of EVs entering in receiving neurons and the components that make EVs toxic, we aim to characterize firstly, how the glia-to-neurons miscommunication contributes to neurodegeneration and then how to detect the toxic components in periphery for an early detection of the degenerative processes. Our work comprises a deep proteomics characterization of astrocyte-derived EVs purified from a mouse model of ALS; a complementary validation of the toxic mechanisms induced by EVs in vitro and in vivo, and a pipeline of analysis for plasma ALS EVs (Pasetto et al., Molecular Neurodegeneration, 2021) that is ready to be used to validate the signals from the Central Nervous System to the periphery.
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