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Bassoon proteinopathy drives neurodegeneration in multiple sclerosis

Schattling, Benjamin
Engler, Jan Broder
Volkmann, Constantin
Rothammer, Nicola
Woo, Marcel S
Petersen, Meike
Winkler, Iris
Kaufmann, Max
show hidden authors show all authors [1 - 22]
Published in Nature Neuroscience. 2019, vol. 22, no. 6, p. 887-896
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.
Keywords AnimalsDrosophilaHumansInflammation/metabolism/pathologyMiceMultiple Sclerosis/metabolism/pathologyNerve Degeneration/metabolism/pathologyNerve Tissue Proteins/metabolismNeurons/metabolism/pathologySpinal Cord/metabolism/pathology
PMID: 31011226
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Research group La Sclérose en plaques (908)
FNS: PP00P3_152928
Autre: Helmut Horten Foundation
Autre: Gebert-Rüf Foundation grant no. GRS-049/13
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SCHATTLING, Benjamin et al. Bassoon proteinopathy drives neurodegeneration in multiple sclerosis. In: Nature Neuroscience, 2019, vol. 22, n° 6, p. 887-896. doi: 10.1038/s41593-019-0385-4 https://archive-ouverte.unige.ch/unige:122799

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Deposited on : 2019-09-09

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