UZH is on the trail of a cause of dementia

Zurich – A team at the University of Zurich (UZH) has developed an innovative cell culture model for nerve cells. It shows that there is a connection between a misregulated protein and the death of nerve cells in two neurodegenerative diseases.

Researchers at UZH have developed an innovative 2D cell culture model called iNets that mirrors the properties of the human brain and breaks down complex mechanisms of neurodegeneration. They were supported by the high-density microelectrode arrays (HD-MEAs) from MaxWell Biosystems, a spin-off of the Swiss Federal Institute of Technology in Zurich.

According to a report by the university, they have thus succeeded in identifying a starting point for the treatment of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). This groundbreaking work was led by Dr. Marian Hruska-Plochan (first author) in the group of Prof. Dr. Magdalini Polymenidou (last author) at the UZH Department of Quantitative Biomedicine and published in the journal "Nature".

In ALS, neurons in the motor cortex and spinal cord die off, causing paralysis. FTD, on the other hand, affects brain regions that are responsible for cognition, language and personality. Both are diseases that progress inexorably and for which there are still no effective treatments.

It was known that in both diseases there is an abnormal accumulation of the protein TDP-43 in the neurons of the central nervous system. Using this cell culture model, the UZH study has now been able to decipher that a toxic accumulation of another protein called NPTX2 is responsible for the misbehavior of TDP-43, which in turn leads to the death of the nerve cells.

The team tested these experimental findings on brain tissue from people who had died of ALS or FTD. And indeed, they found that NPTX2 also accumulates here in cells that contain an abnormal accumulation of TDP-43. The iNets cell culture model was therefore able to accurately predict the pathology of ALS and FTD patients.

"The discovery of NPTX2 gives us a clear opportunity to develop a therapeutic that targets the core of the disease," says Magdalini Polymenidou. In conjunction with two other target molecules recently identified by other research teams, a combination therapy for ALS and FTD would therefore be conceivable. ce/mm

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