Fig. 1.

Summary of the findings by Baughn et al. In neurons of healthy individuals, TDP-43 is located predominantly in the nucleus and binds to STMN2 pre-mRNA preventing inclusion of deleterious exon 2a. Nuclear loss of TDP-43 in vulnerable neurons occurs in a variety of neurodegenerative diseases, and inclusion of exon 2a in mature STMN2 mRNA leads to the loss of STMN2 protein important for axon maintenance and regeneration. In STMN2 pre-mRNA processing, TDP-43 acts as a steric block preventing access of the splicing machinery to exon 2a. This function of TDP-43 can be replaced, e.g., by antisense oligonucleotides (ASOs), and expression of STMN2 protein restored