Abstract

This talk will summarise my lab's recent progress in understanding mechanisms of neurodegeneration and how this is informing new therapeutic approaches. The central concept is the identification of common pathways across the spectrum of these disorders (which include Alzheimer's and related diseases) relevant for both mechanistic insights and therapy. I will focus on data showing the importance of one such pathway: dysregulated signalling through the Unfolded Protein Response (UPR). I will highlight specifically the PERK branch of the UPR and its role in controlling global protein synthesis rates critical for neuronal health, particularly in the . I will present data from preclinical models showing that genetic and pharmacological manipulation of the pathway is profoundly neuroprotective in several mouse models of neurodegeneration, and discuss the recent discovery of repurposed drugs ready for clinical trials and future directions.