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ARUK 2023 | Investigating TDP-43 pathology with cryptic exons

Matthew Keuss, PhD, UCL Queen Square Institute of Neurology, University College London, London, discusses the potential value of studying cryptic exons to shed light on the pathophysiological mechanisms of TDP-43 loss in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Cryptic exons are formed as a consequence of TDP-43 aggregation, as its neuronal loss leads to mis-splicing events and the improper inclusion of intronic sequences. Dr Keuss notes that these sequences could be used as readouts in high-throughput assays, their presence reflective of loss of function of TDP-43. Identifying key upstream events that promote pathological TDP-43 phase transition and aggregation is an important next step for novel target discovery. This interview took place at the Alzheimer’s Research UK (ARUK) Conference 2023 in Aberdeen, UK.

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