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GLOCALIST, daily newspaper for innovation

Multiple sclerosis (MS) is characterized by inflammation of the brain tissue, leading to progressive damage to the nerve cells. "Exactly how nerve cells react to inflammation has been difficult to study," explains Prof. dr. with. Manuel Friese, Head of the Institute for Neuroimmunology and Multiple Sclerosis of UKE, who deals with the mechanisms of nerve cell death in MS.

Only new molecular biology methods made it possible for the Prof. Friese team to gain insight into the nerve cells' response patterns that are exposed to inflammatory stress. In addition, the researchers observed changes in a number of genetic programs.

"A central response from the neurons was the activation of the cell's own waste disposal machines," Dr. Dr. Jan Broder Engler, Institute of Neuroimmunology and Multiple Sclerosis, who conducted bioinformatic analyzes. This is needed to break down accumulations of damaged or defective proteins, which can otherwise lead to cell damage. For this purpose, the researchers observed an accumulation of protein phage in the nerve cells.

Although faeces occur naturally in neurons, inflammation led to a redistribution and massive accumulation of the protein. "Similar toxic protein accumulations were already known in neurogenic diseases, such as Alzheimer's or Parkinson's," Dr. Benjamin Schattling, Institute of Neuroimmunology and Multiple Sclerosis. Finding such changes now in MS was surprising for the team and at the same time opened a new therapeutic starting point.

"Our goal was to eliminate the toxic protein aggregates," says prof. Friese. This was finally achieved with a substance that improves the disposal of impaired proteins and thus protects the nerve cells from destruction. With the new results achieved, the researchers in UKE hope to develop new treatment methods in multiple sclerosis. These are particularly necessary in the late stage of the disease, where current immunotherapies are no longer effective.

Publication: Bass 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. 201

9. * Both authors contributed equally. DOI: https://doi.org/10.1038/s41593-019-0385-4

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