Bibliographic Details
| Title: |
Bassoon proteinopathy drives neurodegeneration in multiple sclerosis. |
| Authors: |
Schattling, Benjamin (AUTHOR), Engler, Jan Broder (AUTHOR), Volkmann, Constantin (AUTHOR), Rothammer, Nicola (AUTHOR), Woo, Marcel S. (AUTHOR), Petersen, Meike (AUTHOR), Winkler, Iris (AUTHOR), Kaufmann, Max (AUTHOR), Rosenkranz, Sina C. (AUTHOR), Fejtova, Anna (AUTHOR), Thomas, Ulrich (AUTHOR), Bose, Aparajita (AUTHOR), Bauer, Simone (AUTHOR), Träger, Simone (AUTHOR), Miller, Katharine K. (AUTHOR), Brück, Wolfgang (AUTHOR), Duncan, Kent E. (AUTHOR), Salinas, Gabriela (AUTHOR), Soba, Peter (AUTHOR), Gundelfinger, Eckart D. (AUTHOR) |
| Source: |
Nature Neuroscience. Jun2019, Vol. 22 Issue 6, p887-896. 10p. 6 Color Photographs, 1 Diagram. |
| Abstract: |
Multiple sclerosis (MS) is characterized by inflammatory insults that drive neuroaxonal injury. However, knowledge about neuron-intrinsic responses to inflammation is limited. By leveraging neuron-specific messenger RNA profiling, we found that neuroinflammation leads to induction and toxic accumulation of the synaptic protein bassoon (Bsn) in the neuronal somata of mice and patients with MS. Neuronal overexpression of Bsn in flies resulted in reduction of lifespan, while genetic disruption of Bsn protected mice from inflammation-induced neuroaxonal injury. Notably, pharmacological proteasome activation boosted the clearance of accumulated Bsn and enhanced neuronal survival. Our study demonstrates that neuroinflammation initiates toxic protein accumulation in neuronal somata and advocates proteasome activation as a potential remedy. The authors report that the presynaptic protein bassoon forms toxic aggregates in neuronal somata in multiple sclerosis. Stimulation of proteasomal activity reduces bassoon aggregates, neuroaxonal loss and disability during CNS inflammation. [ABSTRACT FROM AUTHOR] |
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| Database: |
Psychology and Behavioral Sciences Collection |
