A protein called TDP-43 is frequently found in nerve cells of the central nervous system of patients with ALS or FTD. The Zurich researchers wanted to elucidate the cellular mechanism and used a 2D cell culture for this purpose.
It is called iNETS (interconnected neuronal networks) and based on patient skin cells that have been reprogrammed into neurons and their supporting cells. This also made it possible to investigate the development of TDP-43 dysfunction through to neurodegeneration of the nerve cells.

They found another protein called NPTX2 as a link to the dysfunction of TDP-43, which was also found in conspiciously high amounts of brain cells of deceased ALS patients.

The protein NPTX2 is now considered a promising therapeutic target for the treatment of ALS and FTD.

Original publication in Nature:
Hruska-Plochan M, Wiersma VI, Betz KM, Mallona I, Ronchi S, Maniecka Z, Hock EM, Tantardini E, Laferriere F, Sahadevan S, Hoop V, Delvendahl I, Pérez-Berlanga M, Gatta B, Panatta M, van der Bourg A, Bohaciakova D, Sharma P, De Vos L, Frontzek K, Aguzzi A, Lashley T, Robinson MD, Karayannis T, Mueller M, Hierlemann A, Polymenidou M. (2024). A model of human neural networks reveals NPTX2 pathology in ALS and FTLD. Nature. 2024 Feb 14. doi: 10.1038/s41586-024-07042-7. Epub ahead of print. PMID: 38355792.

Further information:
https://www.news.uzh.ch/de/articles/media/2024/Neurodegeneration.html