Project description:
Multiple sclerosis (MS) is an autoimmune inflammatory disease of the brain and spinal cord. A chronic inflammatory response in the central nervous system leads to a continuous loss of neurons, which current therapies cannot prevent. In this study, the scientists discovered that protein degradation through the so-called proteasome is dramatically reduced in inflamed nerve cells. This impaired degradation results in the accumulation of proteins that are normally continuously broken down. Among these are proteins that alter the metabolism of nerve cells, ultimately causing them to degenerate. By genetically or pharmacologically modulating protein degradation and metabolism, it is possible to slow the loss of neurons in preclinical MS models. This represents a promising new approach to counteracting neuronal loss in inflammatory diseases.
Publication:
Woo MS, Brand J, Bal LC, Moritz M, Walkenhorst M, Vieira V, Ipenberg I, Rothammer N, Wang M, Dogan B, Loreth D, Mayer C, Nagel D, Wagner I, Pfeffer LK, Landgraf P, van Ham M, Mattern KMJ, Winschel I, Frantz N, Sonner JK, Grosshans HK, Miguela A, Bauer S, Meurs N, Müller A, Binkle-Ladisch L, Salinas G, Jänsch L, Dieterich DC, Riedner M, Krüger E, Heppner FL, Glatzel M, Puelles VG, Engler JB, Nyengaard JR, Misgeld T, Kerschensteiner M, Merkler D, Meyer-Schwesinger C, Friese MA. The immunoproteasome disturbs neuronal metabolism and drives neurodegeneration in multiple sclerosis. Cell. 2025 Aug
Submitting the Paper of the Month:
Else Kröner-Fresenius-Stiftung is using the series “Paper of the Month” to report in an exemplary and hot-off-the-press style on the outstanding work being done by the scientists it supports. We regularly present publications which have recently appeared in especially renowned journals, have emerged from foundation funding and been given appropriate acknowledgment. This is done in the respective categories “Original Paper” and “Review”. In the case of each of these publications, the first author and/or senior author are being funded by the foundation.
We invite all project managers, fellowship recipients and members of graduate study programs to send their work in accordance with the stated criteria as proposal for Paper of the Month to Ms. Anne Asschenfeldt (a.asschenfeldt@ekfs.de).
More Paper of the Month can be found here.
