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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, Rosenkranz, Sina C., Fejtova, Anna, Thomas, Ulrich, Bose, Aparajita, Bauer, Simone, Träger, Simone, Miller, Katharine K., Brück, Wolfgang, Duncan, Kent E., Salinas, Gabriela, Soba, Peter, Gundelfinger, Eckart D., Merkler, Doron, Friese, Manuel A.·2019·Nature Neuroscience
DOI 10.1038/s41593-019-0385-4
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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.

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  1. Friese, M. A., Schattling, B. & Fugger, L. Mechanisms of neurodegeneration and axonal dysfunction in multiple sclerosis. Nat. Rev. Neurol. 10, 225–238 (2014). · DOI · Paper page
  2. Campbell, G. R. et al. Mitochondrial DNA deletions and neurodegeneration in multiple sclerosis. Ann. Neurol. 69, 481–492 (2011). · DOI
  3. Forte, M. et al. Cyclophilin D inactivation protects axons in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. Proc. Natl Acad. Sci. USA 104, 7558–7563 (2007). · DOI
  4. Weisfeld-Adams, J. D., Katz Sand, I. B., Honce, J. M. & Lublin, F. D. Differential diagnosis of Mendelian and mitochondrial disorders in patients with suspected multiple sclerosis. Brain 138, 517–539 (2015). · DOI
  5. Schattling, B. et al. TRPM4 cation channel mediates axonal and neuronal degeneration in experimental autoimmune encephalomyelitis and multiple sclerosis. Nat. Med. 18, 1805–1811 (2012). · DOI
  6. Friese, M. A. et al. Acid-sensing ion channel-1 contributes to axonal degeneration in autoimmune inflammation of the central nervous system. Nat. Med. 13, 1483–1489 (2007). · DOI
  7. Schattling, B. et al. Activity of NaV1.2 promotes neurodegeneration in an animal model of multiple sclerosis. JCI Insight 1, e89810 (2016). · DOI
  8. Bading, H. Nuclear calcium signalling in the regulation of brain function. Nat. Rev. Neurosci. 14, 593–608 (2013). · DOI
  9. Raddatz, B. B. et al. Transcriptomic meta-analysis of multiple sclerosis and its experimental models. PLoS One 9, e86643 (2014). · DOI
  10. Schmidt, E. F. et al. Identification of the cortical neurons that mediate antidepressant responses. Cell 149, 1152–1163 (2012). · DOI
  11. Thomson, S. R. et al. Cell-type-specific translation profiling reveals a novel strategy for treating fragile X syndrome. Neuron 95, 550–563.e5 (2017). · DOI
  12. Sun, S. et al. Translational profiling identifies a cascade of damage initiated in motor neurons and spreading to glia in mutant SOD1-mediated ALS. Proc. Natl Acad. Sci. USA 112, E6993–E7002 (2015). · DOI
  13. Brichta, L. et al. Identification of neurodegenerative factors using translatome-regulatory network analysis. Nat. Neurosci. 18, 1325–1333 (2015). · DOI · Paper page
  14. Chiti, F. & Dobson, C. M. Protein misfolding, amyloid formation, and human disease: a summary of progress over the last decade. Annu. Rev. Biochem. 86, 27–68 (2017). · DOI · Paper page
  15. Cho, H. et al. Differential innate immune response programs in neuronal subtypes determine susceptibility to infection in the brain by positive-stranded RNA viruses. Nat. Med. 19, 458–464 (2013). · DOI · Paper page
  16. Han, M. H. et al. Janus-like opposing roles of CD47 in autoimmune brain inflammation in humans and mice. J. Exp. Med. 209, 1325–1334 (2012). · DOI · Paper page
  17. Gundelfinger, E. D., Reissner, C. & Garner, C. C. Role of Bassoon and Piccolo in assembly and molecular organization of the active zone. Front. Synaptic Neurosci. 7, 19 (2016). · DOI · Paper page
  18. Vucetic, S., Brown, C. J., Dunker, A. K. & Obradovic, Z. Flavors of protein disorder. Proteins 52, 573–584 (2003). · DOI
  19. Macosko, E. Z. et al. Highly parallel genome-wide expression profiling of individual cells using nanoliter droplets. Cell 161, 1202–1214 (2015). · DOI · Paper page
  20. Hetz, C. The unfolded protein response: controlling cell fate decisions under ER stress and beyond. Nat. Rev. Mol. Cell Biol. 13, 89–102 (2012). · DOI
  21. Bruckner, J. J. et al. Fife, a Drosophila Piccolo-RIM homolog, promotes active zone organization and neurotransmitter release. J. Neurosci. 32, 17048–17058 (2012). · DOI
  22. Annamneedi, A. et al. Ablation of the presynaptic organizer Bassoon in excitatory neurons retards dentate gyrus maturation and enhances learning performance. Brain Struct. Funct. 223, 3423–3445 (2018). · DOI
  23. Lee, B. H. et al. Enhancement of proteasome activity by a small-molecule inhibitor of USP14. Nature 467, 179–184 (2010). · DOI · Paper page
  24. Min, J. W., Lü, L., Freeling, J. L., Martin, D. S. & Wang, H. USP14 inhibitor attenuates cerebral ischemia/reperfusion-induced neuronal injury in mice. J. Neurochem. 140, 826–833 (2017). · DOI
  25. Na, C. H. et al. Synaptic protein ubiquitination in rat brain revealed by antibody-based ubiquitome analysis. J. Proteome Res. 11, 4722–4732 (2012). · DOI
  26. Menezes, M. J. et al. Mutation in mitochondrial ribosomal protein S7 (MRPS7) causes congenital sensorineural deafness, progressive hepatic and renal failure and lactic acidemia. Hum. Mol. Genet. 24, 2297–2307 (2015). · DOI
  27. Nikić, I. et al. A reversible form of axon damage in experimental autoimmune encephalomyelitis and multiple sclerosis. Nat. Med. 17, 495–499 (2011). · DOI · Paper page
  28. Popovic, D., Vucic, D. & Dikic, I. Ubiquitination in disease pathogenesis and treatment. Nat. Med. 20, 1242–1253 (2014). · DOI
  29. Lim, J. & Yue, Z. Neuronal aggregates: formation, clearance, and spreading. Dev. Cell 32, 491–501 (2015). · DOI
  30. David, M. A. & Tayebi, M. Detection of protein aggregates in brain and cerebrospinal fluid derived from multiple sclerosis patients. Front. Neurol. 5, 251 (2014). · DOI
  31. Jarosz, D. F. & Khurana, V. Specification of physiologic and disease states by distinct proteins and protein conformations. Cell 171, 1001–1014 (2017). · DOI
  32. Yabe, I. et al. Mutations in bassoon in individuals with familial and sporadic progressive supranuclear palsy-like syndrome. Sci. Rep. 8, 819 (2018). · DOI
  33. Dresbach, T. et al. Assembly of active zone precursor vesicles: obligatory trafficking of presynaptic cytomatrix proteins Bassoon and Piccolo via a trans-Golgi compartment. J. Biol. Chem. 281, 6038–6047 (2006). · DOI
  34. Waites, C. L. et al. Bassoon and Piccolo maintain synapse integrity by regulating protein ubiquitination and degradation. EMBO J. 32, 954–969 (2013). · DOI
  35. Okerlund, N. D. et al. Bassoon controls presynaptic autophagy through Atg5. Neuron 93, 897–913.e7 (2017). · DOI
  36. Harrigan, J. A., Jacq, X., Martin, N. M. & Jackson, S. P. Deubiquitylating enzymes and drug discovery: emerging opportunities. Nat. Rev. Drug Discov. 17, 57–78 (2018). · DOI · Paper page
  37. Walsh, D. M., Tseng, B. P., Rydel, R. E., Podlisny, M. B. & Selkoe, D. J. The oligomerization of amyloid β-protein begins intracellularly in cells derived from human brain. Biochemistry 39, 10831–10839 (2000). · DOI · Paper page
  38. Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15–21 (2013). · DOI · Paper page
  39. Liao, Y., Smyth, G. K. & Shi, W. featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics 30, 923–930 (2014). · DOI · Paper page
  40. Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014). · DOI · Paper page
  41. Durinck, S., Spellman, P. T., Birney, E. & Huber, W. Mapping identifiers for the integration of genomic datasets with the R/Bioconductor package biomaRt. Nat. Protoc. 4, 1184–1191 (2009). · DOI
  42. Chen, J., Bardes, E. E., Aronow, B. J. & Jegga, A. G. ToppGene Suite for gene list enrichment analysis and candidate gene prioritization. Nucleic Acids Res. 37, W305–W311 (2009). · DOI · Paper page
  43. Peng, K., Radivojac, P., Vucetic, S., Dunker, A. K. & Obradovic, Z. Length-dependent prediction of protein intrinsic disorder. BMC Bioinformatics 7, 208 (2006). · DOI
  44. Dresbach, T. et al. Functional regions of the presynaptic cytomatrix protein bassoon: significance for synaptic targeting and cytomatrix anchoring. Mol. Cell. Neurosci. 23, 279–291 (2003). · DOI
  45. Chien, C. L., Lu, K. S., Lin, Y. S., Hsieh, C. J. & Hirokawa, N. The functional cooperation of MAP1A heavy chain and light chain 2 in the binding of microtubules. Exp. Cell Res. 308, 446–458 (2005). · DOI
  46. Kowalczyk, M. S. et al. Single-cell RNA-seq reveals changes in cell cycle and differentiation programs upon aging of hematopoietic stem cells. Genome Res. 25, 1860–1872 (2015). · DOI · Paper page
  47. Han, C., Jan, L. Y. & Jan, Y. N. Enhancer-driven membrane markers for analysis of nonautonomous mechanisms reveal neuron-glia interactions in Drosophila. Proc. Natl Acad. Sci. USA 108, 9673–9678 (2011). · DOI
  48. Sun, Y. et al. Aging studies in Drosophila melanogaster. Methods Mol. Biol. 1048, 77–93 (2013). · DOI

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Metadata

Authors
Schattling, B., Engler, J. B., Volkmann, C., Rothammer, N., Woo, M. S., Petersen, M., Winkler, I., Kaufmann, M., Rosenkranz, S. C., Fejtova, A., Thomas, U., Bose, A., Bauer, S., Träger, S., Miller, K. K., Brück, W., Duncan, K. E., Salinas, G., Soba, P., Gundelfinger, E. D., Merkler, D., & Friese, M. A.
ORCID
Venue
Nature Neuroscience
Publisher
Springer Science and Business Media LLC
Published
2019-04-22
Volume
22
Issue
6
Pages
887-896
ISSN
  • 1097-6256
  • 1546-1726
DOI
10.1038/s41593-019-0385-4
Cited by
86
References
16
Language
en
Licence
www.springer.com/tdm (tdm)

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