The RSC Jeremy Knowles Award Lecture - Adapting the Chemistry and/or Biology of Proteostasis to Ameliorate Protein Aggregation Diseases

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• Jeffery W. Kelly, Departments of Chemistry and Molecular Medicine, and The Skaggs Institute of Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Rd., La Jolla, CA 92037
• Friday 23 February 2018, 16:30-17:30
• Wolfson Lecture Theatre, Department of Chemistry.

If you have a question about this talk, please contact Priyanka Joshi.

The cellular protein homeostasis, or proteostasis network, regulates proteome function by controlling ribosomal protein synthesis, chaperone and chaperonin mediated protein folding, protein trafficking, protein degradation and related processes. Stress responsive signaling pathways match proteostasis network capacity with demand in each subcellular compartment to maintain or alter cellular homeostasis. The beginning of the seminar will focus on how the proteostasis network can be adapted pharmacologically through stress responsive signaling to alleviate the gain-of-toxic-function diseases, including light chain amyloidosis and the transthyretin amyloidosis, where excessive secretion of misfolding and aggregation of proteins leads to a degenerative phenotypes. We will also cover our efforts towards the discovery of autophagy activators for ameliorating the Tauopathies. These drug candidates are envisioned to be generally useful for ameliorating multiple neurodegenerative diseases based on human genetic evidence. These strategies will be contrasted with high affinity small molecule binding to the normally folded structural ensemble of an aggregation-prone protein inside and/or outside of the cell to stabilize the native state, lowering the population of misfolded, misassembly competent states that lead to aggregates, including amyloid fibrils. Our progress towards discovering light chain and transthyretin kinetic stabilizers will be covered.

This talk is part of the Department of Chemistry series.

This talk is included in these lists:

• Department of Chemistry
• Wolfson Lecture Theatre, Department of Chemistry

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