{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:19:30Z","timestamp":1790813970131,"version":"4.1.0"},"reference-count":106,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2020,1,13]],"date-time":"2020-01-13T00:00:00Z","timestamp":1578873600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2020,1,13]],"date-time":"2020-01-13T00:00:00Z","timestamp":1578873600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR\u201010\u2010LABX\u20100030\u2010INRT"],"award-info":[{"award-number":["ANR\u201010\u2010LABX\u20100030\u2010INRT"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR\u201010\u2010IDEX\u20100002\u201002"],"award-info":[{"award-number":["ANR\u201010\u2010IDEX\u20100002\u201002"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["ERC\u20102012\u2010StG #310659"],"award-info":[{"award-number":["ERC\u20102012\u2010StG #310659"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["EMBO J"],"published-print":{"date-parts":[[2020,2,17]]},"DOI":"10.15252\/embj.2018100574","type":"journal-article","created":{"date-parts":[[2020,1,13]],"date-time":"2020-01-13T05:32:50Z","timestamp":1578893570000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":146,"title":["Reduced autophagy upon C9ORF72 loss synergizes with dipeptide repeat protein toxicity in G4C2 repeat expansion disorders"],"prefix":"10.1038","volume":"39","author":[{"given":"Manon","family":"Boivin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Pfister","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angeline","family":"Gaucherot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Ruffenach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc","family":"Negroni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantal","family":"Sellier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4423-4920","authenticated-orcid":false,"given":"Nicolas","family":"Charlet\u2010Berguerand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,1,13]]},"reference":[{"key":"BFEMBJ2018100574_CR1","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1007\/s00401-013-1149-y","volume":"126","author":"S Almeida","year":"2013","unstructured":"Almeida S, Gascon E, Tran H, Chou HJ, Gendron TF, Degroot S, Tapper AR, Sellier C, Charlet\u2010Berguerand N, Karydas A et\u00a0al (2013) Modeling key pathological features of frontotemporal dementia with C9ORF72 repeat expansion in iPSC\u2010derived human neurons. Acta Neuropathol 126: 385\u2013399","journal-title":"Acta Neuropathol"},{"key":"BFEMBJ2018100574_CR2","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1007\/s00401-019-02083-z","volume":"138","author":"S Almeida","year":"2019","unstructured":"Almeida S, Krishnan G, Rushe M, Gu Y, Kankel MW, Gao FB (2019) Production of poly(GA) in C9ORF72 patient motor neurons derived from induced pluripotent stem cells. Acta Neuropathol 138: 1099\u20131101","journal-title":"Acta Neuropathol"},{"key":"BFEMBJ2018100574_CR3","doi-asserted-by":"crossref","first-page":"3040","DOI":"10.1091\/mbc.e16-01-0003","volume":"27","author":"J Amick","year":"2016","unstructured":"Amick J, Roczniak\u2010Ferguson A, Ferguson SM (2016) C9orf72 binds SMCR8, localizes to lysosomes, and regulates mTORC1 signaling. Mol Biol Cell 27: 3040\u20133051","journal-title":"Mol Biol Cell"},{"key":"BFEMBJ2018100574_CR4","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/j.neuron.2013.02.004","volume":"77","author":"PE Ash","year":"2013","unstructured":"Ash PE, Bieniek KF, Gendron TF, Caulfield T, Lin WL, van Blitterswijk MM, Jansen\u2010West K, Paul JW III, Rademakers R, Boylan KB et\u00a0al (2013) Unconventional translation of C9ORF72 GGGGCC expansion generates insoluble polypeptides specific to c9FTD\/ALS. Neuron 77: 639\u2013646","journal-title":"Neuron"},{"key":"BFEMBJ2018100574_CR5","doi-asserted-by":"crossref","first-page":"23204","DOI":"10.1038\/srep23204","volume":"16","author":"A Atanasio","year":"2016","unstructured":"Atanasio A, Decman V, White D, Ramos M, Ikiz B, Lee HC, Siao CJ, Brydges S, LaRosa E, Bai Y et\u00a0al (2016) C9orf72 ablation causes immune dysregulation characterized by leukocyte expansion, autoantibody production, and glomerulonephropathy in mice. Sci Rep 16: 23204","journal-title":"Sci Rep"},{"key":"BFEMBJ2018100574_CR6","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1038\/nchembio.1563","volume":"10","author":"SJ Barmada","year":"2014","unstructured":"Barmada SJ, Serio A, Arjun A, Bilican B, Daub A, Ando DM, Tsvetkov A, Pleiss M, Li X, Peisach D et\u00a0al (2014) Autophagy induction enhances TDP43 turnover and survival in neuronal ALS models. Nat Chem Biol 10: 677\u2013685","journal-title":"Nat Chem Biol"},{"key":"BFEMBJ2018100574_CR7","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1007\/s00401-015-1480-6","volume":"130","author":"M van Blitterswijk","year":"2015","unstructured":"van Blitterswijk M, Gendron TF, Baker MC, DeJesus\u2010Hernandez M, Finch NA, Brown PH, Daughrity LM, Murray ME, Heckman MG, Jiang J et\u00a0al (2015) Novel clinical associations with specific C9ORF72 transcripts in patients with repeat expansions in C9ORF72. Acta Neuropathol 130: 863\u2013876","journal-title":"Acta Neuropathol"},{"key":"BFEMBJ2018100574_CR8","doi-asserted-by":"crossref","first-page":"20877","DOI":"10.1038\/srep20877","volume":"12","author":"S Boeynaems","year":"2016","unstructured":"Boeynaems S, Bogaert E, Michiels E, Gijselinck I, Sieben A, Jovi\u010di\u0107 A, De Baets G, Scheveneels W, Steyaert J, Cuijt I et\u00a0al (2016) Drosophila screen connects nuclear transport genes to DPR pathology in c9ALS\/FTD. Sci Rep 12: 20877","journal-title":"Sci Rep"},{"key":"BFEMBJ2018100574_CR9","doi-asserted-by":"crossref","first-page":"347ra93","DOI":"10.1126\/scitranslmed.aaf6038","volume":"8","author":"A Burberry","year":"2016","unstructured":"Burberry A, Suzuki N, Wang JY, Moccia R, Mordes DA, Stewart MH, Suzuki\u2010Uematsu S, Ghosh S, Singh A, Merkle FT et\u00a0al (2016) Loss\u2010of\u2010function mutations in the C9ORF72 mouse ortholog cause fatal autoimmune disease. Sci Transl Med 8: 347ra93","journal-title":"Sci Transl Med"},{"key":"BFEMBJ2018100574_CR10","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.4161\/auto.25188","volume":"9","author":"K Castillo","year":"2013","unstructured":"Castillo K, Nassif M, Valenzuela V, Rojas F, Matus S, Mercado G, Court FA, van Zundert B, Hetz C (2013) Trehalose delays the progression of amyotrophic lateral sclerosis by enhancing autophagy in motoneurons. Autophagy 9: 1308\u20131320","journal-title":"Autophagy"},{"key":"BFEMBJ2018100574_CR11","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/s41467-017-02495-z","volume":"9","author":"W Cheng","year":"2018","unstructured":"Cheng W, Wang S, Mestre AA, Fu C, Makarem A, Xian F, Hayes LR, Lopez\u2010Gonzalez R, Drenner K, Jiang J et\u00a0al (2018) C9ORF72 GGGGCC repeat\u2010associated non\u2010AUG translation is upregulated by stress through eIF2\u03b1 phosphorylation. Nat Commun 9: 51","journal-title":"Nat Commun"},{"key":"BFEMBJ2018100574_CR12","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1126\/science.aaa9344","volume":"348","author":"J Chew","year":"2015","unstructured":"Chew J, Gendron TF, Prudencio M, Sasaguri H, Zhang YJ, Castanedes\u2010Casey M, Lee CW, Jansen\u2010West K, Kurti A, Murray ME et\u00a0al (2015) C9ORF72 repeat expansions in mice cause TDP\u201043 pathology, neuronal loss, and behavioral deficits. Science 348: 1151\u20131154","journal-title":"Science"},{"key":"BFEMBJ2018100574_CR13","doi-asserted-by":"crossref","first-page":"2794","DOI":"10.1038\/s41467-018-05273-7","volume":"9","author":"M Chitiprolu","year":"2018","unstructured":"Chitiprolu M, Jagow C, Tremblay V, Bondy\u2010Chorney E, Paris G, Savard A, Palidwor G, Barry FA, Zinman L, Keith J et\u00a0al (2018) A complex of C9ORF72 and p62 uses arginine methylation to eliminate stress granules by autophagy. Nat Commun 9: 2794","journal-title":"Nat Commun"},{"key":"BFEMBJ2018100574_CR14","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1038\/s41593-019-0397-0","volume":"22","author":"SY Choi","year":"2019","unstructured":"Choi SY, Lopez\u2010Gonzalez R, Krishnan G, Phillips HL, Li AN, Seeley WW, Yao WD, Almeida S, Gao FB (2019) C9ORF72\u2010ALS\/FTD\u2010associated poly(GR) binds Atp5a1 and compromises mitochondrial function in\u00a0vivo. Nat Neurosci 22: 851\u2013862","journal-title":"Nat Neurosci"},{"key":"BFEMBJ2018100574_CR201","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1002\/ana.23946","volume":"74","author":"S Ciura","year":"2013","unstructured":"Ciura S, Lattante S, Le Ber I, Latouche M, Tostivint H, Brice A, Kabashi E (2013) Loss of function of C9orf72 causes motor deficits in a zebrafish model of amyotrophic lateral sclerosis. Ann Neurol 74: 180\u2013187","journal-title":"Ann Neurol"},{"key":"BFEMBJ2018100574_CR15","first-page":"5","volume":"13","author":"EG Conlon","year":"2016","unstructured":"Conlon EG, Lu L, Sharma A, Yamazaki T, Tang T, Shneider NA, Manley JL (2016) The C9ORF72 GGGGCC expansion forms RNA G\u2010quadruplex inclusions and sequesters hnRNP H to disrupt splicing in ALS brains. Elife 13: 5","journal-title":"Elife"},{"key":"BFEMBJ2018100574_CR16","doi-asserted-by":"crossref","first-page":"e37754","DOI":"10.7554\/eLife.37754","volume":"7","author":"EG Conlon","year":"2018","unstructured":"Conlon EG, Fagegaltier D, Agius P, Davis\u2010Porada J, Gregory J, Hubbard I, Kang K, Kim D, New York Genome Center ALS Consortium, Phatnani H et\u00a0al (2018) Unexpected similarities between C9ORF72 and sporadic forms of ALS\/FTD suggest a common disease mechanism. Elife 7: e37754","journal-title":"Elife"},{"issue":"Pt 7","key":"BFEMBJ2018100574_CR17","doi-asserted-by":"crossref","first-page":"2040","DOI":"10.1093\/brain\/awu120","volume":"137","author":"J Cooper\u2010Knock","year":"2014","unstructured":"Cooper\u2010Knock J, Walsh MJ, Higginbottom A, Robin Highley J, Dickman MJ, Edbauer D, Ince PG, Wharton SB, Wilson SA, Kirby J et\u00a0al (2014) Sequestration of multiple RNA recognition motif\u2010containing proteins by C9orf72 repeat expansions. Brain 137(Pt 7): 2040\u20132051","journal-title":"Brain"},{"key":"BFEMBJ2018100574_CR18","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1016\/j.cub.2018.03.063","volume":"28","author":"A Corrionero","year":"2018","unstructured":"Corrionero A, Horvitz HR (2018) A C9orf72 ALS\/FTD ortholog acts in endolysosomal degradation and lysosomal homeostasis. Curr Biol 28: 1522\u20131535.e5","journal-title":"Curr Biol"},{"key":"BFEMBJ2018100574_CR19","doi-asserted-by":"crossref","first-page":"3440","DOI":"10.1093\/hmg\/ddq257","volume":"19","author":"V Crippa","year":"2010","unstructured":"Crippa V, Sau D, Rusmini P, Boncoraglio A, Onesto E, Bolzoni E, Galbiati M, Fontana E, Marino M, Carra S et\u00a0al (2010) The small heat shock protein B8 (HspB8) promotes autophagic removal of misfolded proteins involved in amyotrophic lateral sclerosis (ALS). Hum Mol Genet 19: 3440\u20133456","journal-title":"Hum Mol Genet"},{"key":"BFEMBJ2018100574_CR20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12192-017-0806-9","volume":"23","author":"R Cristofani","year":"2018","unstructured":"Cristofani R, Crippa V, Vezzoli G, Rusmini P, Galbiati M, Cicardi ME, Meroni M, Ferrari V, Tedesco B, Piccolella M et\u00a0al (2018) The small heat shock protein B8 (HSPB8) efficiently removes aggregating species of dipeptides produced in C9ORF72\u2010related neurodegenerative diseases. Cell Stress Chaperones 23: 1\u201312","journal-title":"Cell Stress Chaperones"},{"key":"BFEMBJ2018100574_CR21","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.1002\/stem.2388","volume":"34","author":"R Dafinca","year":"2016","unstructured":"Dafinca R, Scaber J, Ababneh N, Lalic T, Weir G, Christian H, Vowles J, Douglas AG, Fletcher\u2010Jones A, Browne C et\u00a0al (2016) C9orf72 hexanucleotide expansions are associated with altered endoplasmic reticulum calcium homeostasis and stress granule formation in induced pluripotent stem cell\u2010derived neurons from patients with amyotrophic lateral sclerosis and frontotemporal dementia. Stem Cells 34: 2063\u20132078","journal-title":"Stem Cells"},{"key":"BFEMBJ2018100574_CR22","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1111\/nan.12292","volume":"42","author":"Y Davidson","year":"2016","unstructured":"Davidson Y, Robinson AC, Liu X, Wu D, Troakes C, Rollinson S, Masuda\u2010Suzukake M, Suzuki G, Nonaka T, Shi J et\u00a0al (2016) Neurodegeneration in frontotemporal lobar degeneration and motor neurone disease associated with expansions in C9orf72 is linked to TDP\u201043 pathology and not associated with aggregated forms of dipeptide repeat proteins. Neuropathol Appl Neurobiol 42: 242\u2013254","journal-title":"Neuropathol Appl Neurobiol"},{"key":"BFEMBJ2018100574_CR23","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.neuron.2011.09.011","volume":"72","author":"M DeJesus\u2010Hernandez","year":"2011","unstructured":"DeJesus\u2010Hernandez M, Mackenzie IR, Boeve BF, Boxer AL, Baker M, Rutherford NJ, Nicholson AM, Finch NA, Flynn H, Adamson J et\u00a0al (2011) Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p\u2010linked FTD and ALS. Neuron 72: 245\u2013256","journal-title":"Neuron"},{"key":"BFEMBJ2018100574_CR24","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.neuron.2013.10.015","volume":"80","author":"CJ Donnelly","year":"2013","unstructured":"Donnelly CJ, Zhang PW, Pham JT, Heusler AR, Mistry NA, Vidensky S, Daley EL, Poth EM, Hoover B, Fines DM et\u00a0al (2013) RNA toxicity from the ALS\/FTD C9ORF72 expansion is mitigated by antisense intervention. Neuron 80: 415\u2013428","journal-title":"Neuron"},{"key":"BFEMBJ2018100574_CR25","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1038\/nature14974","volume":"525","author":"BD Freibaum","year":"2015","unstructured":"Freibaum BD, Lu Y, Lopez\u2010Gonzalez R, Kim NC, Almeida S, Lee KH, Badders N, Valentine M, Miller BL, Wong PC et\u00a0al (2015) GGGGCC repeat expansion in C9orf72 compromises nucleocytoplasmic transport. Nature 525: 129\u2013133","journal-title":"Nature"},{"key":"BFEMBJ2018100574_CR26","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1186\/s40478-018-0579-0","volume":"6","author":"P Frick","year":"2018","unstructured":"Frick P, Sellier C, Mackenzie IRA, Cheng CY, Tahraoui\u2010Bories J, Martinat C, Pasterkamp RJ, Prudlo J, Edbauer D, Oulad\u2010Abdelghani M et\u00a0al (2018) Novel antibodies reveal presynaptic localization of C9orf72 protein and reduced protein levels in C9orf72 mutation carriers. Acta Neuropathol Commun 6: 72","journal-title":"Acta Neuropathol Commun"},{"key":"BFEMBJ2018100574_CR27","doi-asserted-by":"crossref","first-page":"2208","DOI":"10.1101\/gr.139568.112","volume":"22","author":"C Fritsch","year":"2012","unstructured":"Fritsch C, Herrmann A, Nothnagel M, Szafranski K, Huse K, Schumann F, Schreiber S, Platzer M, Krawczak M, Hampe J et\u00a0al (2012) Genome\u2010wide search for novel human uORFs and N\u2010terminal protein extensions using ribosomal footprinting. Genome Res 22: 2208\u20132218","journal-title":"Genome Res"},{"key":"BFEMBJ2018100574_CR28","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1038\/nrd.2017.22","volume":"16","author":"L Galluzzi","year":"2017","unstructured":"Galluzzi L, Bravo\u2010San Pedro JM, Levine B, Green DR, Kroemer G (2017) Pharmacological modulation of autophagy: therapeutic potential and persisting obstacles. Nat Rev Drug Discov 16: 487\u2013511","journal-title":"Nat Rev Drug Discov"},{"key":"BFEMBJ2018100574_CR29","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1007\/s00401-015-1473-5","volume":"130","author":"P Gami","year":"2015","unstructured":"Gami P, Murray C, Schottlaender L, Bettencourt C, De Pablo Fernandez E, Mudanohwo E, Mizielinska S, Polke JM, Holton JL, Isaacs AM et\u00a0al (2015) A 30\u2010unit hexanucleotide repeat expansion in C9orf72 induces pathological lesions with dipeptide\u2010repeat proteins and RNA foci, but not TDP\u201043 inclusions and clinical disease. Acta Neuropathol 130: 599\u2013601","journal-title":"Acta Neuropathol"},{"key":"BFEMBJ2018100574_CR30","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1016\/j.cell.2017.10.042","volume":"171","author":"FB Gao","year":"2017","unstructured":"Gao FB, Richter JD, Cleveland DW (2017) Rethinking Unconventional Translation in Neurodegeneration. Cell 171: 994\u20131000","journal-title":"Cell"},{"key":"BFEMBJ2018100574_CR31","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1007\/s00401-013-1192-8","volume":"126","author":"TF Gendron","year":"2013","unstructured":"Gendron TF, Bieniek KF, Zhang YJ, Jansen\u2010West K, Ash PE, Caulfield T, Daughrity L, Dunmore JH, Castanedes\u2010Casey M, Chew J et\u00a0al (2013) Antisense transcripts of the expanded C9ORF72 hexanucleotide repeat form nuclear RNA foci and undergo repeat\u2010associated non\u2010ATG translation in c9FTD\/ALS. Acta Neuropathol 126: 829\u2013844","journal-title":"Acta Neuropathol"},{"key":"BFEMBJ2018100574_CR32","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/S1474-4422(11)70261-7","volume":"11","author":"I Gijselinck","year":"2012","unstructured":"Gijselinck I, Van Langenhove T, van der Zee J, Sleegers K, Philtjens S, Kleinberger G, Janssens J, Bettens K, Van Cauwenberghe C, Pereson S et\u00a0al (2012) A C9orf72 promoter repeat expansion in a Flanders\u2010Belgian cohort with disorders of the frontotemporal lobar degeneration\u2010amyotrophic lateral sclerosis spectrum: a gene identification study. Lancet Neurol 11: 54\u201365","journal-title":"Lancet Neurol"},{"key":"BFEMBJ2018100574_CR33","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.1038\/s41467-017-02200-0","volume":"8","author":"KM Green","year":"2017","unstructured":"Green KM, Glineburg MR, Kearse MG, Flores BN, Linsalata AE, Fedak SJ, Goldstrohm AC, Barmada SJ, Todd PK (2017) RAN translation at C9orf72\u2010associated repeat expansions is selectively enhanced by the integrated stress response. Nat Commun 8: 2005","journal-title":"Nat Commun"},{"key":"BFEMBJ2018100574_CR35","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1038\/nature13124","volume":"507","author":"AR Haeusler","year":"2014","unstructured":"Haeusler AR, Donnelly CJ, Periz G, Simko EA, Shaw PG, Kim MS, Maragakis NJ, Troncoso JC, Pandey A, Sattler R et\u00a0al (2014) C9orf72 nucleotide repeat structures initiate molecular cascades of disease. Nature 507: 195\u2013200","journal-title":"Nature"},{"key":"BFEMBJ2018100574_CR36","doi-asserted-by":"crossref","first-page":"2294","DOI":"10.1101\/gad.1830709","volume":"23","author":"C Hetz","year":"2009","unstructured":"Hetz C, Thielen P, Matus S, Nassif M, Court F, Kiffin R, Martinez G, Cuervo AM, Brown RH, Glimcher LH (2009) XBP\u20101 deficiency in the nervous system protects against amyotrophic lateral sclerosis by increasing autophagy. Genes Dev 23: 2294\u20132306","journal-title":"Genes Dev"},{"key":"BFEMBJ2018100574_CR37","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1080\/15548627.2019.1569441","volume":"15","author":"WY Ho","year":"2019","unstructured":"Ho WY, Tai YK, Chang JC, Liang J, Tyan SH, Chen S, Guan JL, Zhou H, Shen HM, Koo E et\u00a0al (2019) The ALS\u2010FTD\u2010linked gene product, C9orf72, regulates neuronal morphogenesis via autophagy. Autophagy 15: 827\u2013842","journal-title":"Autophagy"},{"key":"BFEMBJ2018100574_CR38","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/j.cell.2011.10.002","volume":"147","author":"NT Ingolia","year":"2011","unstructured":"Ingolia NT, Lareau LF, Weissman JS (2011) Ribosome profiling of mouse embryonic stem cells reveals the complexity and dynamics of mammalian proteomes. Cell 147: 789\u2013802","journal-title":"Cell"},{"key":"BFEMBJ2018100574_CR39","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.neuron.2016.04.006","volume":"90","author":"J Jiang","year":"2016","unstructured":"Jiang J, Zhu Q, Gendron TF, Saberi S, McAlonis\u2010Downes M, Seelman A, Stauffer JE, Jafar\u2010Nejad P, Drenner K, Schulte D et\u00a0al (2016) Gain of toxicity from ALS\/FTD\u2010linked repeat expansions in C9ORF72 Is alleviated by antisense oligonucleotides targeting GGGGCC\u2010containing RNAs. Neuron 90: 535\u2013550","journal-title":"Neuron"},{"key":"BFEMBJ2018100574_CR40","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1038\/nn.4085","volume":"18","author":"A Jovi\u010di\u0107","year":"2015","unstructured":"Jovi\u010di\u0107 A, Mertens J, Boeynaems S, Bogaert E, Chai N, Yamada SB, Paul JW III, Sun S, Herdy JR, Bieri G et\u00a0al (2015) Modifiers of C9orf72 dipeptide repeat toxicity connect nucleocytoplasmic transport defects to FTD\/ALS. Nat Neurosci 18: 1226\u20131229","journal-title":"Nat Neurosci"},{"key":"BFEMBJ2018100574_CR41","doi-asserted-by":"crossref","first-page":"e23063","DOI":"10.7554\/eLife.23063","volume":"6","author":"J Jung","year":"2017","unstructured":"Jung J, Nayak A, Schaeffer V, Starzetz T, Kirsch AK, M\u00fcller S, Dikic I, Mittelbronn M, Behrends C (2017) Multiplex image\u2010based autophagy RNAi screening identifies SMCR8 as ULK1 kinase activity and gene expression regulator. Elife 6: e23063","journal-title":"Elife"},{"key":"BFEMBJ2018100574_CR42","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.molcel.2016.02.034","volume":"62","author":"MG Kearse","year":"2016","unstructured":"Kearse MG, Green KM, Krans A, Rodriguez CM, Linsalata AE, Goldstrohm AC, Todd PK (2016) CGG repeat\u2010associated Non\u2010AUG translation utilizes a cap\u2010dependent scanning mechanism of initiation to produce toxic proteins. Mol Cell 62: 314\u2013322","journal-title":"Mol Cell"},{"key":"BFEMBJ2018100574_CR43","first-page":"790","volume":"26","author":"B Khosravi","year":"2017","unstructured":"Khosravi B, Hartmann H, May S, M\u00f6hl C, Ederle H, Michaelsen M, Schludi MH, Dormann D, Edbauer D (2017) Cytoplasmic poly\u2010GA aggregates impair nuclear import of TDP\u201043 in C9orf72 ALS\/FTLD. Hum Mol Genet 26: 790\u2013800","journal-title":"Hum Mol Genet"},{"key":"BFEMBJ2018100574_CR44","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1002\/ana.24453","volume":"78","author":"M Koppers","year":"2015","unstructured":"Koppers M, Blokhuis AM, Westeneng HJ, Terpstra ML, Zundel CA, Vieira de S\u00e1 R, Schellevis RD, Waite AJ, Blake DJ, Veldink JH et\u00a0al (2015) C9orf72 ablation in mice does not cause motor neuron degeneration or motor deficits. Ann Neurol 78: 426\u2013438","journal-title":"Ann Neurol"},{"key":"BFEMBJ2018100574_CR45","first-page":"5073","volume":"9","author":"M Kozak","year":"1989","unstructured":"Kozak M (1989) Context effects and inefficient initiation at non\u2010AUG codons in eucaryotic cell\u2010free translation systems. Mol Cell Biol 9: 5073\u20135080","journal-title":"Mol Cell Biol"},{"key":"BFEMBJ2018100574_CR46","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1126\/science.1254917","volume":"345","author":"I Kwon","year":"2014","unstructured":"Kwon I, Xiang S, Kato M, Wu L, Theodoropoulos P, Wang T, Kim J, Yun J, Xie Y, McKnight SL (2014) Poly\u2010dipeptides encoded by the C9orf72 repeats bind nucleoli, impede RNA biogenesis, and kill cells. Science 345: 1139\u20131145","journal-title":"Science"},{"key":"BFEMBJ2018100574_CR47","doi-asserted-by":"crossref","first-page":"E4530","DOI":"10.1073\/pnas.1318835110","volume":"110","author":"C Lagier\u2010Tourenne","year":"2013","unstructured":"Lagier\u2010Tourenne C, Baughn M, Rigo F, Sun S, Liu P, Li HR, Jiang J, Watt AT, Chun S, Katz M et\u00a0al (2013) Targeted degradation of sense and antisense C9orf72 RNA foci as therapy for ALS and frontotemporal degeneration. Proc Natl Acad Sci USA 110: E4530\u2013E4539","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMBJ2018100574_CR48","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1080\/15548627.2019.1569914","volume":"15","author":"Y Lan","year":"2019","unstructured":"Lan Y, Sullivan PM, Hu F (2019) SMCR8 negatively regulates AKT and MTORC1 signaling to modulate lysosome biogenesis and tissue homeostasis. Autophagy 15: 871\u2013885","journal-title":"Autophagy"},{"key":"BFEMBJ2018100574_CR49","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1016\/j.celrep.2013.10.049","volume":"5","author":"YB Lee","year":"2013","unstructured":"Lee YB, Chen HJ, Peres JN, Gomez\u2010Deza J, Attig J, Stalekar M, Troakes C, Nishimura AL, Scotter EL, Vance C et\u00a0al (2013) Hexanucleotide repeats in ALS\/FTD form length\u2010dependent RNA foci, sequester RNA binding proteins, and are neurotoxic. Cell Rep 5: 1178\u20131186","journal-title":"Cell Rep"},{"key":"BFEMBJ2018100574_CR50","doi-asserted-by":"crossref","first-page":"4765","DOI":"10.1093\/hmg\/ddx350","volume":"26","author":"YB Lee","year":"2017","unstructured":"Lee YB, Baskaran P, Gomez\u2010Deza J, Chen HJ, Nishimura AL, Smith BN, Troakes C, Adachi Y, Stepto A, Petrucelli L et\u00a0al (2017) C9orf72 poly GA RAN\u2010translated protein plays a key role in amyotrophic lateral sclerosis via aggregation and toxicity. Hum Mol Genet 26: 4765\u20134777","journal-title":"Hum Mol Genet"},{"key":"BFEMBJ2018100574_CR51","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.neuron.2016.04.005","volume":"90","author":"Y Liu","year":"2016","unstructured":"Liu Y, Pattamatta A, Zu T, Reid T, Bardhi O, Borchelt DR, Yachnis AT, Ranum LP (2016) C9orf72 BAC mouse model with motor deficits and neurodegenerative features of ALS\/FTD. Neuron 90: 521\u2013534","journal-title":"Neuron"},{"key":"BFEMBJ2018100574_CR52","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1212\/WNL.59.7.1077","volume":"59","author":"C Lomen\u2010Hoerth","year":"2002","unstructured":"Lomen\u2010Hoerth C, Anderson T, Miller B (2002) The overlap of amyotrophic lateral sclerosis and frontotemporal dementia. Neurology 59: 1077\u20131079","journal-title":"Neurology"},{"key":"BFEMBJ2018100574_CR53","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.neuron.2016.09.015","volume":"92","author":"R Lopez\u2010Gonzalez","year":"2016","unstructured":"Lopez\u2010Gonzalez R, Lu Y, Gendron TF, Karydas A, Tran H, Yang D, Petrucelli L, Miller BL, Almeida S, Gao FB (2016) Poly(GR) in C9ORF72\u2010Related ALS\/FTD compromises mitochondrial function and increases oxidative stress and DNA damage in iPSC\u2010derived motor neurons. Neuron 92: 383\u2013391","journal-title":"Neuron"},{"key":"BFEMBJ2018100574_CR54","doi-asserted-by":"crossref","first-page":"9628","DOI":"10.1073\/pnas.1901313116","volume":"116","author":"R Lopez\u2010Gonzalez","year":"2019","unstructured":"Lopez\u2010Gonzalez R, Yang D, Pribadi M, Kim TS, Krishnan G, Choi SY, Lee S, Coppola G, Gao FB (2019) Partial inhibition of the overactivated Ku80\u2010dependent DNA repair pathway rescues neurodegeneration in C9ORF72\u2010ALS\/FTD. Proc Natl Acad Sci USA 116: 9628\u20139633","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMBJ2018100574_CR55","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/S1474-4422(12)70043-1","volume":"11","author":"E Majounie","year":"2012","unstructured":"Majounie E, Renton AE, Mok K, Dopper EG, Waite A, Rollinson S, Chi\u00f2 A, Restagno G, Nicolaou N, Simon\u2010Sanchez J et\u00a0al (2012) Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross\u2010sectional study. Lancet Neurol 11: 323\u2013330","journal-title":"Lancet Neurol"},{"key":"BFEMBJ2018100574_CR56","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.stemcr.2017.12.018","volume":"10","author":"L Marrone","year":"2018","unstructured":"Marrone L, Poser I, Casci I, Japtok J, Reinhardt P, Janosch A, Andree C, Lee HO, Moebius C, Koerner E et\u00a0al (2018) Isogenic FUS\u2010eGFP iPSC reporter lines enable quantification of FUS stress granule pathology that is rescued by drugs inducing autophagy. Stem Cell Reports 10: 375\u2013389","journal-title":"Stem Cell Reports"},{"key":"BFEMBJ2018100574_CR57","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s00401-019-01998-x","volume":"138","author":"L Marrone","year":"2019","unstructured":"Marrone L, Drexler HCA, Wang J, Tripathi P, Distler T, Heisterkamp P, Anderson EN, Kour S, Moraiti A, Maharana S et\u00a0al (2019) FUS pathology in ALS is linked to alterations in multiple ALS\u2010associated proteins and rescued by drugs stimulating autophagy. Acta Neuropathol 138: 67\u201384","journal-title":"Acta Neuropathol"},{"key":"BFEMBJ2018100574_CR58","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1007\/s00401-014-1329-4","volume":"128","author":"S May","year":"2014","unstructured":"May S, Hornburg D, Schludi MH, Arzberger T, Rentzsch K, Schwenk BM, Gr\u00e4sser FA, Mori K, Kremmer E, Banzhaf\u2010Strathmann J et\u00a0al (2014) C9orf72 FTLD\/ALS\u2010associated Gly\u2010Ala dipeptide repeat proteins cause neuronal toxicity and Unc119 sequestration. Acta Neuropathol 128: 485\u2013503","journal-title":"Acta Neuropathol"},{"key":"BFEMBJ2018100574_CR202","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1007\/s00401-015-1476-2","volume":"130","author":"IR Mackenzie","year":"2015","unstructured":"Mackenzie IR, Frick P, Gr\u00e4sser FA, Gendron TF, Petrucelli L, Cashman NR, Edbauer D, Kremmer E, Prudlo J, Troost D et\u00a0al (2015) Quantitative analysis and clinico\u2010pathological correlations of different dipeptide repeat protein pathologies in C9ORF72 mutation carriers. Acta Neuropathol 130: 845\u2013861","journal-title":"Acta Neuropathol"},{"key":"BFEMBJ2018100574_CR59","doi-asserted-by":"crossref","first-page":"e323","DOI":"10.1212\/WNL.0000000000004865","volume":"90","author":"P McGoldrick","year":"2018","unstructured":"McGoldrick P, Zhang M, van Blitterswijk M, Sato C, Moreno D, Xiao S, Zhang AB, McKeever PM, Weichert A, Schneider R et\u00a0al (2018) Unaffected mosaic C9orf72 case: RNA foci, dipeptide proteins, but upregulated C9orf72 expression. Neurology 90: e323\u2013e331","journal-title":"Neurology"},{"key":"BFEMBJ2018100574_CR60","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1007\/s00401-013-1200-z","volume":"126","author":"S Mizielinska","year":"2013","unstructured":"Mizielinska S, Lashley T, Norona FE, Clayton EL, Ridler CE, Fratta P, Isaacs AM (2013) C9orf72 frontotemporal lobar degeneration is characterised by frequent neuronal sense and antisense RNA foci. Acta Neuropathol 126: 845\u2013857","journal-title":"Acta Neuropathol"},{"key":"BFEMBJ2018100574_CR61","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1126\/science.1256800","volume":"345","author":"S Mizielinska","year":"2014","unstructured":"Mizielinska S, Gr\u00f6nke S, Niccoli T, Ridler CE, Clayton EL, Devoy A, Moens T, Norona FE, Woollacott IO, Pietrzyk J et\u00a0al (2014) C9orf72 repeat expansions cause neurodegeneration in Drosophila through arginine\u2010rich proteins. Science 345: 1192\u20131194","journal-title":"Science"},{"key":"BFEMBJ2018100574_CR62","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1007\/s00401-017-1798-3","volume":"135","author":"TG Moens","year":"2018","unstructured":"Moens TG, Mizielinska S, Niccoli T, Mitchell JS, Thoeng A, Ridler CE, Gr\u00f6nke S, Esser J, Heslegrave A, Zetterberg H et\u00a0al (2018) Sense and antisense RNA are not toxic in Drosophila models of C9orf72\u2010associated ALS\/FTD. Acta Neuropathol 135: 445\u2013457","journal-title":"Acta Neuropathol"},{"key":"BFEMBJ2018100574_CR63","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1126\/science.1232927","volume":"339","author":"K Mori","year":"2013","unstructured":"Mori K, Weng SM, Arzberger T, May S, Rentzsch K, Kremmer E, Schmid B, Kretzschmar HA, Cruts M, Van Broeckhoven C et\u00a0al (2013) The C9orf72 GGGGCC repeat is translated into aggregating dipeptide\u2010repeat proteins in FTLD\/ALS. Science 339: 1335\u20131338","journal-title":"Science"},{"key":"BFEMBJ2018100574_CR64","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1126\/science.1134108","volume":"314","author":"M Neumann","year":"2006","unstructured":"Neumann M, Sampathu DM, Kwong LK, Truax AC, Micsenyi MC, Chou TT, Bruce J, Schuck T, Grossman M, Clark CM et\u00a0al (2006) Ubiquitinated TDP\u201043 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314: 130\u2013133","journal-title":"Science"},{"key":"BFEMBJ2018100574_CR66","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1126\/science.aaf1064","volume":"351","author":"JG O'Rourke","year":"2016","unstructured":"O'Rourke JG, Bogdanik L, Y\u00e1\u00f1ez A, Lall D, Wolf AJ, Muhammad AK, Ho R, Carmona S, Vit JP, Zarrow J et\u00a0al (2016) C9orf72 is required for proper macrophage and microglial function in mice. Science 351: 1324\u20131329","journal-title":"Science"},{"key":"BFEMBJ2018100574_CR67","doi-asserted-by":"crossref","first-page":"97152","DOI":"10.1172\/jci.insight.97152","volume":"2","author":"SA Patten","year":"2017","unstructured":"Patten SA, Aggad D, Martinez J, Tremblay E, Petrillo J, Armstrong GA, La Fontaine A, Maios C, Liao M, Ciura S et\u00a0al (2017) Neuroleptics as therapeutic compounds stabilizing neuromuscular transmission in amyotrophic lateral sclerosis. JCI Insight 2: 97152","journal-title":"JCI Insight"},{"key":"BFEMBJ2018100574_CR68","doi-asserted-by":"crossref","first-page":"5031","DOI":"10.1016\/S0021-9258(18)83694-8","volume":"264","author":"DS Peabody","year":"1989","unstructured":"Peabody DS (1989) Translation initiation at non\u2010AUG triplets in mammalian cells. J Biol Chem 264: 5031\u20135035","journal-title":"J Biol Chem"},{"key":"BFEMBJ2018100574_CR69","first-page":"1","volume":"5","author":"ND Perera","year":"2017","unstructured":"Perera ND, Sheean RK, Lau CL, Shin YS, Beart PM, Horne MK, Turner BJ (2017) Rilmenidine promotes MTOR\u2010independent autophagy in the mutant SOD1 mouse model of amyotrophic lateral sclerosis without slowing disease progression. Autophagy 5: 1\u201318","journal-title":"Autophagy"},{"key":"BFEMBJ2018100574_CR70","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1016\/j.neuron.2015.11.018","volume":"88","author":"OM Peters","year":"2015","unstructured":"Peters OM, Cabrera GT, Tran H, Gendron TF, McKeon JE, Metterville J, Weiss A, Wightman N, Salameh J, Kim J et\u00a0al (2015) Human C9ORF72 hexanucleotide expansion reproduces RNA foci and dipeptide repeat proteins but not neurodegeneration in BAC transgenic mice. Neuron 88: 902\u2013909","journal-title":"Neuron"},{"key":"BFEMBJ2018100574_CR71","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.neuron.2011.09.010","volume":"72","author":"AE Renton","year":"2011","unstructured":"Renton AE, Majounie E, Waite A, Sim\u00f3n\u2010S\u00e1nchez J, Rollinson S, Gibbs JR, Schymick JC, Laaksovirta H, van Swieten JC, Myllykangas L et\u00a0al (2011) A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21\u2010linked ALS\/FTD. Neuron 72: 257\u2013268","journal-title":"Neuron"},{"key":"BFEMBJ2018100574_CR72","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1212\/01.wnl.0000172911.39167.b6","volume":"65","author":"GM Ringholz","year":"2005","unstructured":"Ringholz GM, Appel SH, Bradshaw M, Cooke NA, Mosnik DM, Schulz PE (2005) Prevalence and patterns of cognitive impairment in sporadic ALS. Neurology 65: 586\u2013590","journal-title":"Neurology"},{"key":"BFEMBJ2018100574_CR73","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1038\/nrd3802","volume":"11","author":"DC Rubinsztein","year":"2012","unstructured":"Rubinsztein DC, Codogno P, Levine B (2012) Autophagy modulation as a potential therapeutic target for diverse diseases. Nat Rev Drug Discov 11: 709\u2013730","journal-title":"Nat Rev Drug Discov"},{"key":"BFEMBJ2018100574_CR74","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1007\/s00401-017-1793-8","volume":"135","author":"S Saberi","year":"2017","unstructured":"Saberi S, Stauffer JE, Jiang J, Garcia SD, Taylor AE, Schulte D, Ohkubo T, Schloffman CL, Maldonado M, Baughn M et\u00a0al (2017) Sense\u2010encoded poly\u2010GR dipeptide repeat proteins correlate to neurodegeneration and uniquely co\u2010localize with TDP\u201043 in dendrites of repeat\u2010expanded C9orf72 amyotrophic lateral sclerosis. Acta Neuropathol 135: 459\u2013474","journal-title":"Acta Neuropathol"},{"key":"BFEMBJ2018100574_CR75","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/s00401-017-1711-0","volume":"134","author":"MH Schludi","year":"2017","unstructured":"Schludi MH, Becker L, Garrett L, Gendron TF, Zhou Q, Schreiber F, Popper B, Dimou L, Strom TM, Winkelmann J et\u00a0al (2017) Spinal poly\u2010GA inclusions in a C9orf72 mouse model trigger motor deficits and inflammation without neuron loss. Acta Neuropathol 134: 241\u2013254","journal-title":"Acta Neuropathol"},{"key":"BFEMBJ2018100574_CR76","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.15252\/embj.201593350","volume":"35","author":"C Sellier","year":"2016","unstructured":"Sellier C, Campanari ML, Corbier C, Gaucherot A, Kolb\u2010Cheynel I, Oulad\u2010Abdelghani M, Ruffenach F, Page A, Ciura S, Kabashi E et\u00a0al (2016) Loss of C9ORF72 partly impairs autophagy and synergizes the toxicity of Ataxin\u20102 with intermediate size of polyglutamine expansion. EMBO J 35: 1276\u20131297","journal-title":"EMBO J"},{"key":"BFEMBJ2018100574_CR77","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.neuron.2016.12.016","volume":"93","author":"C Sellier","year":"2017","unstructured":"Sellier C, Buijsen RA, He F, Natla S, Jung L, Tropel P, Gaucherot A, Jacobs H, Meziane H, Vincent A et\u00a0al (2017) Translation of expanded CGG repeats into FMRpolyG Is pathogenic and may contribute to fragile X tremor ataxia syndrome. Neuron 93: 331\u2013347","journal-title":"Neuron"},{"key":"BFEMBJ2018100574_CR78","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s40478-019-0685-7","volume":"7","author":"Q Shao","year":"2019","unstructured":"Shao Q, Liang C, Chang Q, Zhang W, Yang M, Chen JF (2019) C9orf72 deficiency promotes motor deficits of a C9ALS\/FTD mouse model in a dose\u2010dependent manner. Acta Neuropathol Commun 7: 32","journal-title":"Acta Neuropathol Commun"},{"key":"BFEMBJ2018100574_CR79","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/nm.4490","volume":"24","author":"Y Shi","year":"2018","unstructured":"Shi Y, Lin S, Staats KA, Li Y, Chang WH, Hung ST, Hendricks E, Linares GR, Wang Y, Son EY et\u00a0al (2018) Haploinsufficiency leads to neurodegeneration in C9ORF72 ALS\/FTD human induced motor neurons. Nat Med 24: 313\u2013325","journal-title":"Nat Med"},{"key":"BFEMBJ2018100574_CR80","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.nbd.2018.05.009","volume":"116","author":"Y Sonobe","year":"2018","unstructured":"Sonobe Y, Ghadge G, Masaki K, Sendoel A, Fuchs E, Roos RP (2018) Translation of dipeptide repeat proteins from the C9ORF72 expanded repeat is associated with cellular stress. Neurobiol Dis 116: 155\u2013165","journal-title":"Neurobiol Dis"},{"key":"BFEMBJ2018100574_CR81","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/s00401-016-1581-x","volume":"132","author":"E Sudria\u2010Lopez","year":"2016","unstructured":"Sudria\u2010Lopez E, Koppers M, de Wit M, van der Meer C, Westeneng HJ, Zundel CA, Youssef SA, Harkema L, de Bruin A, Veldink JH et\u00a0al (2016) Full ablation of C9orf72 in mice causes immune system\u2010related pathology and neoplastic events but no motor neuron defects. Acta Neuropathol 132: 145\u2013147","journal-title":"Acta Neuropathol"},{"key":"BFEMBJ2018100574_CR82","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s40478-016-0324-5","volume":"4","author":"PM Sullivan","year":"2016","unstructured":"Sullivan PM, Zhou X, Robins AM, Paushter DH, Kim D, Smolka MB, Hu F (2016) The ALS\/FTLD associated protein C9orf72 associates with SMCR8 and WDR41 to regulate the autophagy\u2010lysosome pathway. Acta Neuropathol Commun 4: 51","journal-title":"Acta Neuropathol Commun"},{"key":"BFEMBJ2018100574_CR83","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1038\/s41467-017-02643-5","volume":"9","author":"R Tabet","year":"2018","unstructured":"Tabet R, Schaeffer L, Freyermuth F, Jambeau M, Workman M, Lee CZ, Lin CC, Jiang J, Jansen\u2010West K, Abou\u2010Hamdan H et\u00a0al (2018) CUG initiation and frameshifting enable production of dipeptide repeat proteins from ALS\/FTD C9ORF72 transcripts. Nat Commun 9: 152","journal-title":"Nat Commun"},{"key":"BFEMBJ2018100574_CR84","doi-asserted-by":"crossref","first-page":"2426","DOI":"10.1093\/hmg\/ddv005","volume":"24","author":"Z Tao","year":"2015","unstructured":"Tao Z, Wang H, Xia Q, Li K, Li K, Jiang X, Xu G, Wang G, Ying Z (2015) Nucleolar stress and impaired stress granule formation contribute to C9orf72 RAN translation\u2010induced cytotoxicity. Hum Mol Genet 24: 2426\u20132441","journal-title":"Hum Mol Genet"},{"key":"BFEMBJ2018100574_CR85","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.neuron.2013.03.026","volume":"78","author":"PK Todd","year":"2013","unstructured":"Todd PK, Oh SY, Krans A, He F, Sellier C, Frazer M, Renoux AJ, Chen KC, Scaglione KM, Basrur V et\u00a0al (2013) CGG repeat\u2010associated translation mediates neurodegeneration in fragile X tremor ataxia syndrome. Neuron 78: 440\u2013455","journal-title":"Neuron"},{"key":"BFEMBJ2018100574_CR86","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1016\/j.neuron.2015.09.015","volume":"87","author":"H Tran","year":"2015","unstructured":"Tran H, Almeida S, Moore J, Gendron TF, Chalasani U, Lu Y, Du X, Nickerson JA, Petrucelli L, Weng Z et\u00a0al (2015) Differential toxicity of nuclear RNA foci versus dipeptide repeat proteins in a Drosophila model of C9ORF72 FTD\/ALS. Neuron 87: 1207\u20131214","journal-title":"Neuron"},{"key":"BFEMBJ2018100574_CR87","doi-asserted-by":"crossref","first-page":"16982","DOI":"10.1073\/pnas.1004498107","volume":"107","author":"AS Tsvetkov","year":"2010","unstructured":"Tsvetkov AS, Miller J, Arrasate M, Wong JS, Pleiss MA, Finkbeiner S (2010) A small\u2010molecule scaffold induces autophagy in primary neurons and protects against toxicity in a Huntington disease model. Proc Natl Acad Sci USA 107: 16982\u201316987","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMBJ2018100574_CR88","doi-asserted-by":"crossref","first-page":"e1006443","DOI":"10.1371\/journal.pgen.1006443","volume":"12","author":"J Ugolino","year":"2016","unstructured":"Ugolino J, Ji YJ, Conchina K, Chu J, Nirujogi RS, Pandey A, Brady NR, Hamacher\u2010Brady A, Wang J (2016) Loss of C9orf72 enhances autophagic activity via deregulated mTOR and TFEB signaling. PLoS Genet 12: e1006443","journal-title":"PLoS Genet"},{"key":"BFEMBJ2018100574_CR89","doi-asserted-by":"crossref","first-page":"589","DOI":"10.3389\/fnins.2018.00589","volume":"12","author":"A Viod\u00e9","year":"2018","unstructured":"Viod\u00e9 A, Fournier C, Camuzat A, Fenaille F, NeuroCEB Brain Bank, Latouche M, Elahi F, Le Ber I, Junot C, Lamari F et\u00a0al (2018) New antibody\u2010free mass spectrometry\u2010based quantification reveals that C9ORF72 long protein isoform is reduced in the frontal cortex of hexanucleotide\u2010repeat expansion carriers. Front Neurosci 12: 589.","journal-title":"Front Neurosci"},{"key":"BFEMBJ2018100574_CR90","doi-asserted-by":"crossref","first-page":"1779.e5","DOI":"10.1016\/j.neurobiolaging.2014.01.016","volume":"35","author":"AJ Waite","year":"2014","unstructured":"Waite AJ, B\u00e4umer D, East S, Neal J, Morris HR, Ansorge O, Blake DJ (2014) Reduced C9orf72 protein levels in frontal cortex of amyotrophic lateral sclerosis and frontotemporal degeneration brain with the C9ORF72 hexanucleotide repeat expansion. Neurobiol Aging 35: 1779.e5\u20131779.e13","journal-title":"Neurobiol Aging"},{"key":"BFEMBJ2018100574_CR91","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1038\/nn.4604","volume":"20","author":"C Walker","year":"2017","unstructured":"Walker C, Herranz\u2010Martin S, Karyka E, Liao C, Lewis K, Elsayed W, Lukashchuk V, Chiang SC, Ray S, Mulcahy PJ et\u00a0al (2017) C9orf72 expansion disrupts ATM\u2010mediated chromosomal break repair. Nat Neurosci 20: 1225\u20131235","journal-title":"Nat Neurosci"},{"key":"BFEMBJ2018100574_CR92","doi-asserted-by":"crossref","first-page":"15024","DOI":"10.1073\/pnas.1206362109","volume":"109","author":"IF Wang","year":"2012","unstructured":"Wang IF, Guo BS, Liu YC, Wu CC, Yang CH, Tsai KJ, Shen CK (2012) Autophagy activators rescue and alleviate pathogenesis of a mouse model with proteinopathies of the TAR DNA\u2010binding protein 43. Proc Natl Acad Sci USA 109: 15024\u201315029","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMBJ2018100574_CR93","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.15252\/embj.201694401","volume":"35","author":"CP Webster","year":"2016","unstructured":"Webster CP, Smith EF, Bauer CS, Moller A, Hautbergue GM, Ferraiuolo L, Myszczynska MA, Higginbottom A, Walsh MJ, Whitworth AJ et\u00a0al (2016) The C9orf72 protein interacts with Rab1a and the ULK1 complex to regulate initiation of autophagy. EMBO J 35: 1656\u20131676","journal-title":"EMBO J"},{"key":"BFEMBJ2018100574_CR94","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1016\/j.neuron.2014.12.010","volume":"84","author":"X Wen","year":"2014","unstructured":"Wen X, Tan W, Westergard T, Krishnamurthy K, Markandaiah SS, Shi Y, Lin S, Shneider NA, Monaghan J, Pandey UB et\u00a0al (2014) Antisense proline\u2010arginine RAN dipeptides linked to C9ORF72\u2010ALS\/FTD form toxic nuclear aggregates that initiate in\u00a0vitro and in\u00a0vivo neuronal death. Neuron 84: 1213\u20131225","journal-title":"Neuron"},{"key":"BFEMBJ2018100574_CR95","doi-asserted-by":"crossref","first-page":"e9423","DOI":"10.15252\/emmm.201809423","volume":"11","author":"T Westergard","year":"2019","unstructured":"Westergard T, McAvoy K, Russell K, Wen X, Pang Y, Morris B, Pasinelli P, Trotti D, Haeusler A (2019) Repeat\u2010associated non\u2010AUG translation in C9orf72\u2010ALS\/FTD is driven by neuronal excitation and stress. EMBO Mol Med 11: e9423","journal-title":"EMBO Mol Med"},{"key":"BFEMBJ2018100574_CR96","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/j.molcel.2019.03.019","volume":"74","author":"MR White","year":"2019","unstructured":"White MR, Mitrea DM, Zhang P, Stanley CB, Cassidy DE, Nourse A, Phillips AH, Tolbert M, Taylor JP, Kriwacki RW (2019) C9orf72 Poly(PR) dipeptide repeats disturb biomolecular phase separation and disrupt nucleolar function. Mol Cell 74: 713\u2013728.e6","journal-title":"Mol Cell"},{"key":"BFEMBJ2018100574_CR97","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1002\/ana.24469","volume":"78","author":"S Xiao","year":"2015","unstructured":"Xiao S, MacNair L, McGoldrick P, McKeever PM, McLean JR, Zhang M, Keith J, Zinman L, Rogaeva E, Robertson J (2015) Isoform\u2010specific antibodies reveal distinct subcellular localizations of C9orf72 in amyotrophic lateral sclerosis. Ann Neurol 78: 568\u2013583","journal-title":"Ann Neurol"},{"key":"BFEMBJ2018100574_CR98","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.brainres.2016.04.062","volume":"15","author":"S Xiao","year":"2016","unstructured":"Xiao S, MacNair L, McLean J, McGoldrick P, McKeever P, Soleimani S, Keith J, Zinman L, Rogaeva E, Robertson J (2016) C9orf72 isoforms in amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Brain Res 15: 43\u201349","journal-title":"Brain Res"},{"key":"BFEMBJ2018100574_CR99","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1093\/hmg\/ddu576","volume":"24","author":"M Yamakawa","year":"2015","unstructured":"Yamakawa M, Ito D, Honda T, Kubo K, Noda M, Nakajima K, Suzuki N (2015) Characterization of the dipeptide repeat protein in the molecular pathogenesis of c9FTD\/ALS. Hum Mol Genet 24: 1630\u20131645","journal-title":"Hum Mol Genet"},{"key":"BFEMBJ2018100574_CR100","doi-asserted-by":"crossref","first-page":"e1601167","DOI":"10.1126\/sciadv.1601167","volume":"2","author":"M Yang","year":"2016","unstructured":"Yang M, Liang C, Swaminathan K, Herrlinger S, Lai F, Shiekhattar R, Chen JF (2016) A C9ORF72\/SMCR8\u2010containing complex regulates ULK1 and plays a dual role in autophagy. Sci Adv 2: e1601167","journal-title":"Sci Adv"},{"key":"BFEMBJ2018100574_CR101","doi-asserted-by":"crossref","first-page":"412","DOI":"10.4161\/auto.7.4.14541","volume":"7","author":"X Zhang","year":"2011","unstructured":"Zhang X, Li L, Chen S, Yang D, Wang Y, Zhang X, Wang Z, Le W (2011) Rapamycin treatment augments motor neuron degeneration in SOD1(G93A) mouse model of amyotrophic lateral sclerosis. Autophagy 7: 412\u2013425","journal-title":"Autophagy"},{"key":"BFEMBJ2018100574_CR103","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/nature14973","volume":"525","author":"K Zhang","year":"2015","unstructured":"Zhang K, Donnelly CJ, Haeusler AR, Grima JC, Machamer JB, Steinwald P, Daley EL, Miller SJ, Cunningham KM, Vidensky S et\u00a0al (2015) The C9orf72 repeat expansion disrupts nucleocytoplasmic transport. Nature 525: 56\u201361","journal-title":"Nature"},{"key":"BFEMBJ2018100574_CR104","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1038\/nn.4272","volume":"19","author":"YJ Zhang","year":"2016","unstructured":"Zhang YJ, Gendron TF, Grima JC, Sasaguri H, Jansen\u2010West K, Xu YF, Katzman RB, Gass J, Murray ME, Shinohara M et\u00a0al (2016) C9ORF72 poly(GA) aggregates sequester and impair HR23 and nucleocytoplasmic transport proteins. Nat Neurosci 19: 668\u2013677","journal-title":"Nat Neurosci"},{"key":"BFEMBJ2018100574_CR105","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1038\/s41591-018-0071-1","volume":"24","author":"YJ Zhang","year":"2018","unstructured":"Zhang YJ, Gendron TF, Ebbert MTW, O'Raw AD, Yue M, Jansen\u2010West K, Zhang X, Prudencio M, Chew J, Cook CN et\u00a0al (2018) Poly(GR) impairs protein translation and stress granule dynamics in C9orf72\u2010associated frontotemporal dementia and amyotrophic lateral sclerosis. Nat Med 24: 1136\u20131142","journal-title":"Nat Med"},{"key":"BFEMBJ2018100574_CR106","doi-asserted-by":"crossref","first-page":"eaav2606","DOI":"10.1126\/science.aav2606","volume":"363","author":"YJ Zhang","year":"2019","unstructured":"Zhang YJ, Guo L, Gonzales PK, Gendron TF, Wu Y, Jansen\u2010West K, O'Raw AD, Pickles SR, Prudencio M, Carlomagno Y et\u00a0al (2019) Heterochromatin anomalies and double\u2010stranded RNA accumulation underlie C9orf72 poly(PR) toxicity. Science 363: eaav2606","journal-title":"Science"},{"key":"BFEMBJ2018100574_CR107","doi-asserted-by":"crossref","first-page":"E4968","DOI":"10.1073\/pnas.1302825110","volume":"110","author":"T Zu","year":"2013","unstructured":"Zu T, Liu Y, Ba\u00f1ez\u2010Coronel M, Reid T, Pletnikova O, Lewis J, Miller TM, Harms MB, Falchook AE, Subramony SH et\u00a0al (2013) RAN proteins and RNA foci from antisense transcripts in C9ORF72 ALS and frontotemporal dementia. Proc Natl Acad Sci USA 110: E4968\u2013E4977","journal-title":"Proc Natl Acad Sci USA"}],"container-title":["The EMBO Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.15252\/embj.2018100574.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.15252\/embj.2018100574","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.15252\/embj.2018100574\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.embopress.org\/doi\/pdf\/10.15252\/embj.2018100574","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.15252\/embj.2018100574.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T20:00:37Z","timestamp":1779307237000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.15252\/embj.2018100574"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,13]]},"references-count":106,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2020,2,17]]}},"alternative-id":["BFEMBJ2018100574"],"URL":"https:\/\/doi.org\/10.15252\/embj.2018100574","relation":{},"ISSN":["0261-4189","1460-2075"],"issn-type":[{"value":"0261-4189","type":"print"},{"value":"1460-2075","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,13]]},"assertion":[{"value":"27 August 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 November 2019","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 December 2019","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 January 2020","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"EMBJ2018100574"}}