Protein accumulation damages nerve cells in multiple sclerosis

Multiple sclerosis (MS) is characterized by inflammation in brain and spinal cord tissue leading to progressive damage of nerve cells. “How exactly the nerve cells react to inflammation has so far been difficult to investigate” explains Prof. Dr. Manuel Friese, Director of the Institute of Neuroimmunology and Multiple Sclerosis at the UKE. Only new molecular biology methods enabled Prof. Friese’s team to gain insights into the reaction patterns of nerve cells exposed to inflammatory stress. The researchers observed changes in a number of genetic programs.

“A central reaction of the nerve cells was the activation of the cell’s own machinery for waste disposal,” said Dr. Dr. Jan Broder Engler, Institute of Neuroimmunology and Multiple Sclerosis, who carried out the bioinformatic analyses. This is required to break down accumulations of damaged or misfolded proteins that can otherwise lead to cell damage. In keeping with this, the researchers observed an accumulation of the protein bassoon in the nerve cell bodies. Although bassoon also occurs naturally in nerve cells, inflammation led to redistribution and massive accumulation of the protein. “Similar toxic protein accumulations were already known in neurogenerative diseases such as Alzheimer’s or Parkinson’s,” said Dr. Benjamin Schattling, Institute of Neuroimmunology and Multiple Sclerosis. The team was surprised to find such changes in MS, which opened up a new therapeutic approach.

“Our goal was to eliminate the toxic protein aggregates,” said Prof. Friese. This was finally achieved with a substance that improves the disposal of proteins labelled for degradation and thus protects the nerve cells from destruction. The scientists at the UKE hope that the new findings will enable them to develop new treatment methods for MS. These are particularly needed in the late stage of the disease, in which current immunotherapies are not effective.

In addition to the UKE, the Leibniz-Institut für Neurobiologie Magdeburg, the Friedrich-Alexander-Universität Erlangen-Nürnberg, the Georg-August-Universität Göttingen and the University of Geneva have also been involved.

contact for scientific information:
Prof. Dr. Manuel Friese
Institut für Neuroimmunologie und Multiple Sklerose
Universitätsklinikum Hamburg-Eppendorf (UKE)
Martinistraße 52
20246 Hamburg
Telefon: 040 7410-57277
m.friese@uke.de

original publication:
Bassoon proteinopathy drives neurodegeneration in multiple sclerosis. Benjamin Schattling*, Jan Broder Engler*, Constantin Volkmann, Nicola Rothammer, Marcel S. Woo, Meike Petersen, Iris Winkler, Max Kaufmann, Sina C. Rosenkranz, Anna Fejtova, Ulrich Thomas, Aparajita Bose, Simone Bauer, Simone Träger, Katharine K. Miller, Wolfgang Brück, Kent E. Duncan, Gabriela Salinas, Peter Soba, Eckart D. Gundelfinger, Doron Merkler and Manuel A. Friese. Nature Neuroscience. 2019. *both authors contributed equally.
DOI: https://doi.org/10.1038/s41593-019-0385-4

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