Cofilin hyperphosphorylation triggers TDP-43 pathology in sporadic amyotrophic lateral sclerosis
Cyril J. Jagaraj·Julie D. Atkin·Sina Shadfar·Prachi Mehta·Kuok Yap·Sara Assar Kashani·Marta Vidal·Thomas Fath·Sayanthooran Saravanabavan·David J. Craik·Sonam Parakh·Alexandra K. Suchowerska·Shashi Gautam·Mrithulabashini Jayakumar·Audrey M G Ragagnin·Fabiha Farzana·Md Shafi Jamali·Shu Yang
Pathological forms of TAR-binding protein 43 (TDP-43), involving its aberrant mislocalization to the cytoplasm, inclusion formation, hyperphosphorylation and fragmentation, are present in ∼45-50% frontotemporal dementia (FTD) and Alzheimer's disease individuals, and most (97%) amyotrophic lateral sclerosis (ALS) cases. Hence, identifying mechanisms that induce TDP-43 pathology are central to neurodegeneration and developing new therapeutic targets in these conditions. Cofilin is a multi-function