| Literature DB >> 31011226 |
Benjamin Schattling1, Jan Broder Engler1, Constantin Volkmann1, Nicola Rothammer1, Marcel S Woo1, Meike Petersen2, Iris Winkler1, Max Kaufmann1, Sina C Rosenkranz1, Anna Fejtova3,4, Ulrich Thomas3, Aparajita Bose1, Simone Bauer1, Simone Träger1, Katharine K Miller2, Wolfgang Brück5, Kent E Duncan2, Gabriela Salinas6, Peter Soba2, Eckart D Gundelfinger3,7, Doron Merkler8, Manuel A Friese9.
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.Entities:
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Year: 2019 PMID： 31011226 DOI： 10.1038/s41593-019-0385-4
Source DB: PubMed Journal: Nat Neurosci ISSN： 1097-6256 Impact factor: 28.771