Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comment
. 2023 Jul 12;8(1):266.
doi: 10.1038/s41392-023-01533-1.

Restoring expression of Stathmin-2: a novel strategy to treat TDP-43 proteinopathies

Sonja Menge #  1 , Lorena Decker #  1 , Axel Freischmidt  2
Affiliations
Comment

Restoring expression of Stathmin-2: a novel strategy to treat TDP-43 proteinopathies

Sonja Menge et al. Signal Transduct Target Ther. .
No abstract available

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
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
See this image and copyright information in PMC

Comment on

  • Mechanism of STMN2 cryptic splice-polyadenylation and its correction for TDP-43 proteinopathies.
    Baughn MW, Melamed Z, López-Erauskin J, Beccari MS, Ling K, Zuberi A, Presa M, Gonzalo-Gil E, Maimon R, Vazquez-Sanchez S, Chaturvedi S, Bravo-Hernández M, Taupin V, Moore S, Artates JW, Acks E, Ndayambaje IS, Agra de Almeida Quadros AR, Jafar-Nejad P, Rigo F, Bennett CF, Lutz C, Lagier-Tourenne C, Cleveland DW. Baughn MW, et al. Science. 2023 Mar 17;379(6637):1140-1149. doi: 10.1126/science.abq5622. Epub 2023 Mar 16. Science. 2023. PMID: 36927019 Free PMC article.

References

    1. Baughn MW, et al. Mechanism of STMN2 cryptic splice-polyadenylation and its correction for TDP-43 proteinopathies. Science. 2023;379:1140–1149. doi: 10.1126/science.abq5622. - DOI - PMC - PubMed
    1. Guerra San Juan I, et al. Loss of mouse Stmn2 function causes motor neuropathy. Neuron. 2022;110:1671–1688.e6. doi: 10.1016/j.neuron.2022.02.011. - DOI - PMC - PubMed
    1. Krus KL, et al. Loss of Stathmin-2, a hallmark of TDP-43-associated ALS, causes motor neuropathy. Cell Rep. 2022;39:111001. doi: 10.1016/j.celrep.2022.111001. - DOI - PMC - PubMed
    1. Melamed Z, et al. Premature polyadenylation-mediated loss of stathmin-2 is a hallmark of TDP-43-dependent neurodegeneration. Nat. Neurosci. 2019;22:180–190. doi: 10.1038/s41593-018-0293-z. - DOI - PMC - PubMed
    1. Lépine S, Castellanos-Montiel MJ, Durcan TM. TDP-43 dysregulation and neuromuscular junction disruption in amyotrophic lateral sclerosis. Transl. Neurodegener. 2022;11:56. doi: 10.1186/s40035-022-00331-z. - DOI - PMC - PubMed

Publication types