; University of Lisbon
Cláudio M. Gomes is Professor of Biochemistry at the Faculty of Sciences, University of Lisbon (Ciências ULisboa), where he coordinates the BioISI research programme on Structure and Function of Biomolecules. His research focuses on protein misfolding and self-assembly in neurodegenerative disease, particularly amyloid and tau aggregation. His work has helped establish S100 proteins as chaperone-like regulators of proteotoxic stress. He obtained his PhD in Biochemistry from NOVA University Lisbon in 1999 through the Gulbenkian PhD Programme in Biology and Medicine, became an independent group leader at ITQB-NOVA in 2003, and was appointed Associate Professor in 2015 and Full Professor in 2023 at Ciências ULisboa
The maintenance of protein homeostasis is fundamental to cellular and organismal health, and its progressive failure is a hallmark of neurodegenerative disease. In Alzheimer’s disease, many of the most pathogenic protein assemblies arise and act in the extracellular space, where they accumulate, disseminate, and trigger toxic and inflammatory responses. Yet although proteostasis has been defined largely through intracellular mechanisms, this raises a central question: how is protein quality control organised beyond the cell? In this seminar, I will present extracellular proteostasis as a systems-level, hierarchical network operating across pericellular, tissue, and systemic tiers. Across these levels, secreted chaperones, proteases, extracellular vesicles, receptors, immune sentinels, and clearance organs cooperate to recognise, buffer, remodel, and remove aberrant protein species. I will then discuss recent work from my laboratory showing that S100 family proteins, and particularly S100B, act as chaperone-like regulators of proteotoxic stress in AD. I will highlight how S100B acts both inside and outside cells to modulate the aggregation, phase separation, toxicity, and propagation of amyloidogenic proteins, particularly tau and amyloid-β, and show how these findings support a more integrated view of proteostasis beyond the cell.
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