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Publication

Investigating the role of mutant TDP-43-ALS using human iPSC-derived motor neurons

Book - Dissertation

TAR DNA binding protein 43 kDa (TDP43) is a major component of pathological inclusions in sporadic and familial amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD-U). Encoded by TARDBP, TDP-43 is a ubiquitously expressed DNA/RNA binding protein. TDP-43 contains 2 RNA recognition motifs, a nuclear localization sequence (NLS), a nuclear export signal, and a glycine-rich C-terminus that mediates protein-protein interactions. TDP-43 predominantly resides in the nucleus, but is capable of nucleocytoplasmic shuttling. In the nucleus, TDP-43 plays a critical role in regulating RNA splicing, as well as modulating microRNA biogenesis. In this project induced pluripotent stem cells (iPSCs) generated from patients with TARDBP mutations and patients with sporadic ALS will be used. For the mutant lines, isogenic control lines will be generated. The iPSCs will be differentiated in spinal motor neurons and used to study phenotypes linked to TDP43 deregulation.
Publication year:2022
Accessibility:Open