A model of human neural networks reveals NPTX2 pathology in ALS and FTLD. (https://pubmed.ncbi.nlm.nih.gov/38355792/)

These scientists wanted to understand a type of disease that affects the brain called TDP-43 proteinopathies. They needed a way to study this disease in the lab using human cells, because the disease works differently in humans than in animals. So, they created special brain cells called iCoMoNSCs using stem cells from humans. These brain cells were very similar to real brain cells and could form connections with each other to create networks, just like in our brains.

The scientists then made some of these brain cells produce too much of a protein called TDP-43, which is linked to the disease. They found that when this happened, the brain cells started to break down and not work properly, leading to damage in the brain. They also discovered that another protein called NPTX2 was involved in this process. When NPTX2 levels were too high, it caused harm to the brain cells. But when they fixed the levels of NPTX2, it helped protect the brain cells from damage caused by TDP-43.

This study showed that there is a connection between TDP-43 and NPTX2 in causing brain damage, which can help scientists find ways to treat these types of diseases in the future.

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., Perez-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. A model of human neural networks reveals NPTX2 pathology in ALS and FTLD. Nature. 2024 Feb 14. doi: 10.1038/s41586-024-07042-7.