UNIGE document Scientific Article
previous document  unige:122799  next document
add to browser collection
Title

Bassoon proteinopathy drives neurodegeneration in multiple sclerosis

Authors
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
Identifiers
PMID: 31011226
Full text
Article (Published version) (3.4 MB) - document accessible for UNIGE members only Limited access to UNIGE
Structures
Research group La Sclérose en plaques (908)
Projects FNS: PP00P3_152928
Helmut Horten Foundation
Gebert-Rüf Foundation grant no. GRS-049/13
Citation
(ISO format)
SCHATTLING, Benjamin et al. Bassoon proteinopathy drives neurodegeneration in multiple sclerosis. In: Nature Neuroscience, 2019, vol. 22, n° 6, p. 887-896. https://archive-ouverte.unige.ch/unige:122799

24 hits

2 downloads

Update

Deposited on : 2019-09-09

Export document
Format :
Citation style :