Len Petrucelli, USA

Presentation:

TAR DNA-binding protein of 43 kDa (TDP-43) is a key player in neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and 50% of cases with frontotemporal dementia (FTD): the protein is mis-localized to the cytoplasm and aggregated in patient brains, leading to a loss of its endogenous activity (1-3). TDP-43 is responsible for suppressing non-canonical cryptic exon (CE) inclusion in target transcripts; accordingly, there is a pathological accumulation of CE-containing transcripts in cases of ALS/FTD and Alzheimer’s disease (AD) with TDP-43 pathology (4-8). The discovery of this cryptic dysregulation has reshaped the way we think about TDP-43 proteinopathies, stimulated biomarker development, and opened new avenues of therapeutic intervention aimed at reversing the missplicing of key targets. Nevertheless, our understanding of the regulation of cryptic splicing, particularly in the absence of TDP-43, remains limited. Dr. Petrucelli will review and present novel findings regarding TDP-43 splicing function and cryptic proteins.

Bio:

Leonard Petrucelli, Ph.D. is currently a consultant and member of the Department of Neuroscience at Mayo Clinic in Florida, where he holds the academic rank of professor of neuroscience and has full faculty privileges in molecular neuroscience at Mayo Graduate School. He is recognized as the Ralph B. and Ruth K. Abrams Professor.