Cell-to-Cell Transmission of Dipeptide Repeat Proteins Linked to C9orf72-ALS/FTD

Cell Reports

Volumn 17, Issue 3, 2016, Pages 645-652

  Westergard, Thomas ^a   Jensen, Brigid K ^a   Wen, Xinmei ^a   Cai, Jingli ^a   Kropf, Elizabeth ^a   Iacovitti, Lorraine ^a   Pasinelli, Piera ^a   Trotti, Davide ^a  

^a THOMAS JEFFERSON UNIVERSITY   (United States)

Author keywords

ALS; C9orf72; cell to cell transmission; dipeptide repeat proteins; DPR; exosomes; FTD; propagation

Indexed keywords

DIPEPTIDE DERIVATIVE; POLY(GLYCINE ALANINE); POLY(GLYCINE ARGININE); POLY(GLYCINE PROLINE); POLY(PROLINE ALANINE); POLY(PROLINE ARGININE); UNCLASSIFIED DRUG; C9ORF72 PROTEIN, HUMAN; DIPEPTIDE; GUANINE NUCLEOTIDE EXCHANGE C9ORF72;

AMYOTROPHIC LATERAL SCLEROSIS; ANIMAL CELL; ARTICLE; C9ORF72 GENE; CELL SPREADING; CELL TRANSPORT; CELLULAR DISTRIBUTION; CONTROLLED STUDY; EXOSOME; FRONTOTEMPORAL DEMENTIA; GENE; GLIA CELL; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; INDUCED PLURIPOTENT STEM CELL; MOTONEURON; NERVE CELL CULTURE; NEUROTRANSMISSION; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; PROTEIN TRANSPORT; RAT; AMINO ACID REPEAT; ANIMAL; CHEMISTRY; GLIA; METABOLISM; NERVE CELL; PATHOLOGY; SPINAL CORD;

AMYOTROPHIC LATERAL SCLEROSIS; ANIMALS; C9ORF72 PROTEIN; DIPEPTIDES; EXOSOMES; FRONTOTEMPORAL DEMENTIA; HUMANS; INDUCED PLURIPOTENT STEM CELLS; MOTOR NEURONS; NEUROGLIA; NEURONS; RATS; REPETITIVE SEQUENCES, AMINO ACID; SPINAL CORD;

EID: 84992187305     PISSN: None     EISSN: 22111247     Source Type: Journal    
DOI: 10.1016/j.celrep.2016.09.032     Document Type: Article

References (36)

1. Ash, P.E., Bieniek, K.F., Gendron, T.F., Caulfield, T., Lin, W.L., Dejesus-Hernandez, M., van Blitterswijk, M.M., Jansen-West, K., Paul, J.W. 3rd, Rademakers, R., et al. Unconventional translation of C9ORF72 GGGGCC expansion generates insoluble polypeptides specific to c9FTD/ALS. Neuron 77 (2013), 639–646.
2. Baborie, A., Griffiths, T.D., Jaros, E., Perry, R., McKeith, I.G., Burn, D.J., Masuda-Suzukake, M., Hasegawa, M., Rollinson, S., Pickering-Brown, S., et al. Accumulation of dipeptide repeat proteins predates that of TDP-43 in frontotemporal lobar degeneration associated with hexanucleotide repeat expansions in C9ORF72 gene. Neuropathol. Appl. Neurobiol. 41 (2015), 601–612.
3. Bellingham, S.A., Guo, B.B., Coleman, B.M., Hill, A.F., Exosomes: vehicles for the transfer of toxic proteins associated with neurodegenerative diseases?. Front. Physiol., 3, 2012, 124.
4. Brettschneider, J., Del Tredici, K., Lee, V.M., Trojanowski, J.Q., Spreading of pathology in neurodegenerative diseases: a focus on human studies. Nat. Rev. Neurosci. 16 (2015), 109–120.
5. Chang, Y.J., Jeng, U.S., Chiang, Y.L., Hwang, I.S., Chen, Y.R., The glycine-alanine dipeptide repeat from C9orf72 hexanucleotide expansions forms toxic amyloids possessing cell-to-cell transmission properties. J. Biol. Chem. 291 (2016), 4903–4911.
6. Ciura, S., Lattante, S., Le Ber, I., Latouche, M., Tostivint, H., Brice, A., Kabashi, E., Loss of function of C9orf72 causes motor deficits in a zebrafish model of amyotrophic lateral sclerosis. Ann. Neurol. 74 (2013), 180–187.
7. Costanzo, M., Zurzolo, C., The cell biology of prion-like spread of protein aggregates: mechanisms and implication in neurodegeneration. Biochem. J. 452 (2013), 1–17.
8. Danzer, K.M., Kranich, L.R., Ruf, W.P., Cagsal-Getkin, O., Winslow, A.R., Zhu, L., Vanderburg, C.R., McLean, P.J., Exosomal cell-to-cell transmission of alpha synuclein oligomers. Mol. Neurodegener., 7, 2012, 42.
9. DeJesus-Hernandez, M., Mackenzie, I.R., Boeve, B.F., Boxer, A.L., Baker, M., Rutherford, N.J., Nicholson, A.M., Finch, N.A., Flynn, H., Adamson, J., et al. Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 72 (2011), 245–256.
10. Feiler, M.S., Strobel, B., Freischmidt, A., Helferich, A.M., Kappel, J., Brewer, B.M., Li, D., Thal, D.R., Walther, P., Ludolph, A.C., et al. TDP-43 is intercellularly transmitted across axon terminals. J. Cell Biol. 211 (2015), 897–911.
11. Gallegos, S., Pacheco, C., Peters, C., Opazo, C.M., Aguayo, L.G., Features of alpha-synuclein that could explain the progression and irreversibility of Parkinson's disease. Front. Neurosci., 9, 2015, 59.
12. Gendron, T.F., Bieniek, K.F., Zhang, Y.J., Jansen-West, K., Ash, P.E., Caulfield, T., Daughrity, L., Dunmore, J.H., Castanedes-Casey, M., Chew, J., et al. Antisense transcripts of the expanded C9ORF72 hexanucleotide repeat form nuclear RNA foci and undergo repeat-associated non-ATG translation in c9FTD/ALS. Acta Neuropathol. 126 (2013), 829–844.
13. Gendron, T.F., Belzil, V.V., Zhang, Y.J., Petrucelli, L., Mechanisms of toxicity in C9FTLD/ALS. Acta Neuropathol. 127 (2014), 359–376.
14. Gitler, A.D., Tsuiji, H., There has been an awakening: emerging mechanisms of C9orf72 mutations in FTD/ALS. Brain Res. 1647 (2016), 19–29.
15. Kanouchi, T., Ohkubo, T., Yokota, T., Can regional spreading of amyotrophic lateral sclerosis motor symptoms be explained by prion-like propagation?. J. Neurol. Neurosurg. Psychiatry 83 (2012), 739–745.
16. Maury, Y., Côme, J., Piskorowski, R.A., Salah-Mohellibi, N., Chevaleyre, V., Peschanski, M., Martinat, C., Nedelec, S., Combinatorial analysis of developmental cues efficiently converts human pluripotent stem cells into multiple neuronal subtypes. Nat. Biotechnol. 33 (2015), 89–96.
17. May, S., Hornburg, D., Schludi, M.H., Arzberger, T., Rentzsch, K., Schwenk, B.M., Grässer, F.A., Mori, K., Kremmer, E., Banzhaf-Strathmann, J., et al. C9orf72 FTLD/ALS-associated Gly-Ala dipeptide repeat proteins cause neuronal toxicity and Unc119 sequestration. Acta Neuropathol. 128 (2014), 485–503.
18. Mori, K., Arzberger, T., Grässer, F.A., Gijselinck, I., May, S., Rentzsch, K., Weng, S.M., Schludi, M.H., van der Zee, J., Cruts, M., et al. Bidirectional transcripts of the expanded C9orf72 hexanucleotide repeat are translated into aggregating dipeptide repeat proteins. Acta Neuropathol. 126 (2013), 881–893.
19. Mori, K., Weng, S.M., Arzberger, T., May, S., Rentzsch, K., Kremmer, E., Schmid, B., Kretzschmar, H.A., Cruts, M., Van Broeckhoven, C., et al. The C9orf72 GGGGCC repeat is translated into aggregating dipeptide-repeat proteins in FTLD/ALS. Science 339 (2013), 1335–1338.
20. Nath, S., Agholme, L., Kurudenkandy, F.R., Granseth, B., Marcusson, J., Hallbeck, M., Spreading of neurodegenerative pathology via neuron-to-neuron transmission of β-amyloid. J. Neurosci. 32 (2012), 8767–8777.
21. Pant, S., Hilton, H., Burczynski, M.E., The multifaceted exosome: biogenesis, role in normal and aberrant cellular function, and frontiers for pharmacological and biomarker opportunities. Biochem. Pharmacol. 83 (2012), 1484–1494.
22. Proudfoot, M., Gutowski, N.J., Edbauer, D., Hilton, D.A., Stephens, M., Rankin, J., Mackenzie, I.R., Early dipeptide repeat pathology in a frontotemporal dementia kindred with C9ORF72 mutation and intellectual disability. Acta Neuropathol. 127 (2014), 451–458.
23. Raposo, G., Stoorvogel, W., Extracellular vesicles: exosomes, microvesicles, and friends. J. Cell Biol. 200 (2013), 373–383.
24. Ren, P.H., Lauckner, J.E., Kachirskaia, I., Heuser, J.E., Melki, R., Kopito, R.R., Cytoplasmic penetration and persistent infection of mammalian cells by polyglutamine aggregates. Nat. Cell Biol. 11 (2009), 219–225.
25. Renton, A.E., Majounie, E., Waite, A., Simón-Sánchez, J., Rollinson, S., Gibbs, J.R., Schymick, J.C., Laaksovirta, H., van Swieten, J.C., Myllykangas, L., et al., ITALSGEN Consortium. A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron 72 (2011), 257–268.
26. Saman, S., Kim, W., Raya, M., Visnick, Y., Miro, S., Saman, S., Jackson, B., McKee, A.C., Alvarez, V.E., Lee, N.C., Hall, G.F., Exosome-associated tau is secreted in tauopathy models and is selectively phosphorylated in cerebrospinal fluid in early Alzheimer disease. J. Biol. Chem. 287 (2012), 3842–3849.
27. Schipper, L.J., Raaphorst, J., Aronica, E., Baas, F., de Haan, R., de Visser, M., Troost, D., Prevalence of brain and spinal cord inclusions, including dipeptide repeat proteins, in patients with the C9ORF72 hexanucleotide repeat expansion: a systematic neuropathological review. Neuropathol. Appl. Neurobiol., 2015, 10.1111/nan.12284 Published online September 16, 2015.
28. Schludi, M.H., May, S., Grässer, F.A., Rentzsch, K., Kremmer, E., Küpper, C., Klopstock, T., Arzberger, T., Edbauer, D. German Consortium for Frontotemporal Lobar Degeneration, Bavarian Brain Banking Alliance. Distribution of dipeptide repeat proteins in cellular models and C9orf72 mutation cases suggests link to transcriptional silencing. Acta Neuropathol. 130 (2015), 537–555.
29. Silverman, J.M., Fernando, S.M., Grad, L.I., Hill, A.F., Turner, B.J., Yerbury, J.J., Cashman, N.R., Disease mechanisms in ALS: misfolded SOD1 transferred through exosome-dependent and exosome-independent pathways. Cell. Mol. Neurobiol. 36 (2016), 377–381.
30. Su, Z., Zhang, Y., Gendron, T.F., Bauer, P.O., Chew, J., Yang, W.Y., Fostvedt, E., Jansen-West, K., Belzil, V.V., Desaro, P., et al. Discovery of a biomarker and lead small molecules to target r(GGGGCC)-associated defects in c9FTD/ALS. Neuron 83 (2014), 1043–1050.
31. Therrien, M., Rouleau, G.A., Dion, P.A., Parker, J.A., Deletion of C9ORF72 results in motor neuron degeneration and stress sensitivity in C. elegans. PLoS ONE, 8, 2013, e83450.
32. Théry, C., Amigorena, S., Raposo, G., Clayton, A., Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Curr. Protoc. Cell Biol., 30, 2006 3.22.1–3.22.29.
33. Wen, X., Tan, W., Westergard, T., Krishnamurthy, K., Markandaiah, S.S., Shi, Y., Lin, S., Shneider, N.A., Monaghan, J., Pandey, U.B., et al. Antisense proline-arginine RAN dipeptides linked to C9ORF72-ALS/FTD form toxic nuclear aggregates that initiate in vitro and in vivo neuronal death. Neuron 84 (2014), 1213–1225.
34. Zhang, Y.J., Jansen-West, K., Xu, Y.F., Gendron, T.F., Bieniek, K.F., Lin, W.L., Sasaguri, H., Caulfield, T., Hubbard, J., Daughrity, L., et al. Aggregation-prone c9FTD/ALS poly(GA) RAN-translated proteins cause neurotoxicity by inducing ER stress. Acta Neuropathol. 128 (2014), 505–524.
35. Zhang, Y.J., Gendron, T.F., Grima, J.C., Sasaguri, H., Jansen-West, K., Xu, Y.F., Katzman, R.B., Gass, J., Murray, M.E., Shinohara, M., et al. C9ORF72 poly(GA) aggregates sequester and impair HR23 and nucleocytoplasmic transport proteins. Nat. Neurosci. 19 (2016), 668–677.
36. Zu, T., Liu, Y., Bañez-Coronel, M., Reid, T., Pletnikova, O., Lewis, J., Miller, T.M., Harms, M.B., Falchook, A.E., Subramony, S.H., et al. RAN proteins and RNA foci from antisense transcripts in C9ORF72 ALS and frontotemporal dementia. Proc. Natl. Acad. Sci. USA 110 (2013), E4968–E4977.