{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T23:07:41Z","timestamp":1792624061593,"version":"4.5.0"},"reference-count":79,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2023,5,27]],"date-time":"2023-05-27T00:00:00Z","timestamp":1685145600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,5,27]],"date-time":"2023-05-27T00:00:00Z","timestamp":1685145600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100016887","name":"Motor Neurone Disease Research Australia","doi-asserted-by":"publisher","award":["IG1910"],"award-info":[{"award-number":["IG1910"]}],"id":[{"id":"10.13039\/100016887","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016887","name":"Motor Neurone Disease Research Australia","doi-asserted-by":"publisher","award":["IG2029"],"award-info":[{"award-number":["IG2029"]}],"id":[{"id":"10.13039\/100016887","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016887","name":"Motor Neurone Disease Research Australia","doi-asserted-by":"publisher","award":["IG2036"],"award-info":[{"award-number":["IG2036"]}],"id":[{"id":"10.13039\/100016887","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016887","name":"Motor Neurone Disease Research Australia","doi-asserted-by":"publisher","award":["IG2221"],"award-info":[{"award-number":["IG2221"]}],"id":[{"id":"10.13039\/100016887","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016887","name":"Motor Neurone Disease Research Australia","doi-asserted-by":"publisher","award":["Phyllis Diana Seman MND Research Grant"],"award-info":[{"award-number":["Phyllis Diana Seman MND Research Grant"]}],"id":[{"id":"10.13039\/100016887","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016887","name":"Motor Neurone Disease Research Australia","doi-asserted-by":"publisher","award":["BLP1901"],"award-info":[{"award-number":["BLP1901"]}],"id":[{"id":"10.13039\/100016887","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016887","name":"Motor Neurone Disease Research Australia","doi-asserted-by":"publisher","award":["IG2308"],"award-info":[{"award-number":["IG2308"]}],"id":[{"id":"10.13039\/100016887","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1095215"],"award-info":[{"award-number":["APP1095215"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1107644"],"award-info":[{"award-number":["APP1107644"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1176913"],"award-info":[{"award-number":["APP1176913"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP2020035"],"award-info":[{"award-number":["APP2020035"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001230","name":"Macquarie University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001230","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Neurobiol"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract\n<\/jats:title><jats:p>Amyotrophic lateral sclerosis (ALS)- and frontotemporal dementia (FTD)-linked mutations in <jats:italic>CCNF<\/jats:italic> have been shown to cause dysregulation to protein homeostasis. <jats:italic>CCNF<\/jats:italic> encodes for cyclin F, which is part of the cyclin F-E3 ligase complex SCF<jats:sup>cyclinF<\/jats:sup> known to ubiquitylate substrates for proteasomal degradation. In this study, we identified a function of cyclin F to regulate substrate solubility and show how cyclin F mechanistically underlies ALS and FTD disease pathogenesis. We demonstrated that ALS and FTD-associated protein sequestosome-1\/p62 (p62) was a canonical substrate of cyclin F which was ubiquitylated by the SCF<jats:sup>cyclinF<\/jats:sup> complex. We found that SCF<jats:sup>cyclin F<\/jats:sup> ubiquitylated p62 at lysine(K)281, and that K281 regulated the propensity of p62 to aggregate. Further, cyclin F expression promoted the aggregation of p62 into the insoluble fraction, which corresponded to an increased number of p62 foci. Notably, ALS and FTD-linked mutant cyclin F p.S621G aberrantly ubiquitylated p62, dysregulated p62 solubility in neuronal-like cells, patient-derived fibroblasts and induced pluripotent stem cells and dysregulated p62 foci formation. Consistently, motor neurons from patient spinal cord tissue exhibited increased p62 ubiquitylation. We suggest that the p.S621G mutation impairs the functions of cyclin F to promote p62 foci formation and shift p62 into the insoluble fraction, which may be associated to aberrant mutant cyclin F-mediated ubiquitylation of p62. Given that p62 dysregulation is common across the ALS and FTD spectrum, our study provides insights into p62 regulation and demonstrates that ALS and FTD-linked cyclin F mutant p.S621G can drive p62 pathogenesis associated with ALS and FTD.<\/jats:p>","DOI":"10.1007\/s12035-023-03355-2","type":"journal-article","created":{"date-parts":[[2023,5,27]],"date-time":"2023-05-27T08:02:02Z","timestamp":1685174522000},"page":"5034-5054","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["The E3 Ubiquitin Ligase SCF Cyclin F Promotes Sequestosome-1\/p62 Insolubility and Foci Formation and is Dysregulated in ALS and FTD Pathogenesis"],"prefix":"10.1007","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7996-1386","authenticated-orcid":false,"given":"Jennilee M.","family":"Davidson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharlynn S. L.","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie L.","family":"Rayner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flora","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberley","family":"Duncan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Russo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Newbery","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunjie","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie M.","family":"Scherer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachelle","family":"Balez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Garc\u00eda-Redondo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"R\u00e1bano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Livia","family":"Rosa-Fernandes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lezanne","family":"Ooi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly L.","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Morsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian P.","family":"Blair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Di Ieva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger S.","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,5,27]]},"reference":[{"issue":"6","key":"3355_CR1","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1007\/s00401-013-1125-6","volume":"125","author":"AM Blokhuis","year":"2013","unstructured":"Blokhuis AM, Groen EJN, Koppers M, van den Berg LH, Pasterkamp RJ (2013) Protein aggregation in amyotrophic lateral sclerosis. Acta Neuropathol 125(6):777\u2013794. https:\/\/doi.org\/10.1007\/s00401-013-1125-6","journal-title":"Acta Neuropathol"},{"key":"3355_CR2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11253","author":"KL Williams","year":"2016","unstructured":"Williams KL et al (2016) CCNF mutations in amyotrophic lateral sclerosis and frontotemporal dementia. Nat Commun. https:\/\/doi.org\/10.1038\/ncomms11253","journal-title":"Nat Commun"},{"key":"3355_CR3","doi-asserted-by":"publisher","unstructured":"Tian D, Li J, Tang L, Zhang N, Fan D (2018) Screening for CCNF mutations in a Chinese amyotrophic lateral sclerosis cohort. Front Aging Neurosci 10. https:\/\/doi.org\/10.3389\/fnagi.2018.00185","DOI":"10.3389\/fnagi.2018.00185"},{"key":"3355_CR4","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1994.tb06955.x","author":"C Bai","year":"1994","unstructured":"Bai C, Richman R, Elledge SJ (1994) Human cyclin F. EMBO J. https:\/\/doi.org\/10.1002\/j.1460-2075.1994.tb06955.x","journal-title":"EMBO J"},{"key":"3355_CR5","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2017.06.011","author":"J Galper","year":"2017","unstructured":"Galper J et al (2017) Cyclin F: a component of an E3 ubiquitin ligase complex with roles in neurodegeneration and cancer. Int J Biochem Cell Biol. https:\/\/doi.org\/10.1016\/j.biocel.2017.06.011","journal-title":"Int J Biochem Cell Biol"},{"key":"3355_CR6","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.18.10453","author":"BA Schulman","year":"1998","unstructured":"Schulman BA, Lindstrom DL, Harlow E (1998) Substrate recruitment to cyclin-dependent kinase 2 by a multipurpose docking site on cyclin A. Proc Natl Acad Sci U S A. https:\/\/doi.org\/10.1073\/pnas.95.18.10453","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"7302","key":"3355_CR7","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1038\/nature09140","volume":"466","author":"V D\u2019Angiolella","year":"2010","unstructured":"D\u2019Angiolella V et al (2010) SCF(Cyclin F) controls centrosome homeostasis and mitotic fidelity through CP110 degradation. Nature 466(7302):138\u2013142. https:\/\/doi.org\/10.1038\/nature09140","journal-title":"Nature"},{"key":"3355_CR8","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.09.019","author":"MJ Emanuele","year":"2011","unstructured":"Emanuele MJ et al (2011) Global identification of modular cullin-RING ligase substrates. Cell. https:\/\/doi.org\/10.1016\/j.cell.2011.09.019","journal-title":"Cell"},{"key":"3355_CR9","doi-asserted-by":"publisher","first-page":"10530","DOI":"10.1038\/ncomms10530","volume":"7","author":"D Walter","year":"2016","unstructured":"Walter D, Hoffmann S, Komseli E-S, Rappsilber J, Gorgoulis V, S\u00f8rensen CS (2016) SCF(Cyclin F)-dependent degradation of CDC6 suppresses DNA re-replication. Nat Commun 7:10530. https:\/\/doi.org\/10.1038\/ncomms10530","journal-title":"Nat Commun"},{"key":"3355_CR10","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2016.09.010","author":"JF Dankert","year":"2016","unstructured":"Dankert JF et al (2016) Cyclin F-mediated degradation of SLBP limits H2A.X accumulation and apoptosis upon genotoxic stress in G2. Mol Cell. https:\/\/doi.org\/10.1016\/j.molcel.2016.09.010","journal-title":"Mol Cell"},{"issue":"5","key":"3355_CR11","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1016\/j.cell.2012.03.043","volume":"149","author":"V D\u2019Angiolella","year":"2012","unstructured":"D\u2019Angiolella V et al (2012) Cyclin F-mediated degradation of ribonucleotide reductase M2 controls genome integrity and DNA repair. Cell 149(5):1023\u20131034. https:\/\/doi.org\/10.1016\/j.cell.2012.03.043","journal-title":"Cell"},{"key":"3355_CR12","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2019.04.010","author":"L Clijsters","year":"2019","unstructured":"Clijsters L et al (2019) Cyclin F controls cell-cycle transcriptional outputs by directing the degradation of the three activator E2Fs. Mol Cell. https:\/\/doi.org\/10.1016\/j.molcel.2019.04.010","journal-title":"Mol Cell"},{"key":"3355_CR13","doi-asserted-by":"publisher","unstructured":"Burdova K et al (2019) E2F1 proteolysis via SCF \u2010cyclin F underlies synthetic lethality between cyclin F loss and Chk1 inhibition. EMBO J. https:\/\/doi.org\/10.15252\/embj.2018101443","DOI":"10.15252\/embj.2018101443"},{"key":"3355_CR14","doi-asserted-by":"publisher","unstructured":"Yuan R et al (2019) Cyclin F\u2010dependent degradation of E2F7 is critical for DNA repair and G2\u2010phase progression. EMBO J. https:\/\/doi.org\/10.15252\/embj.2018101430","DOI":"10.15252\/embj.2018101430"},{"key":"3355_CR15","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2015.05.006","author":"AEH Elia","year":"2015","unstructured":"Elia AEH et al (2015) Quantitative proteomic atlas of ubiquitination and acetylation in the DNA damage response. Mol Cell. https:\/\/doi.org\/10.1016\/j.molcel.2015.05.006","journal-title":"Mol Cell"},{"key":"3355_CR16","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.08.058","author":"R Choudhury","year":"2016","unstructured":"Choudhury R et al (2016) APC\/C and SCFcyclin F constitute a reciprocal feedback circuit controlling S-phase entry. Cell Rep. https:\/\/doi.org\/10.1016\/j.celrep.2016.08.058","journal-title":"Cell Rep"},{"key":"3355_CR17","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-18-1772","author":"RS Deshmukh","year":"2018","unstructured":"Deshmukh RS, Sharma S, Das S (2018) Cyclin F-dependent degradation of RBPJ inhibits IDH1R132H-mediated tumorigenesis. Cancer Res. https:\/\/doi.org\/10.1158\/0008-5472.CAN-18-1772","journal-title":"Cancer Res"},{"key":"3355_CR18","doi-asserted-by":"publisher","unstructured":"Mills CA et al (2020) Sirtuin 5 is regulated by the SCF-Cyclin F ubiquitin ligase and is involved in cell cycle control. Mol Cell Biol 41(2):e00269\u201320. https:\/\/doi.org\/10.1128\/MCB.00269-20","DOI":"10.1128\/MCB.00269-20"},{"key":"3355_CR19","doi-asserted-by":"publisher","unstructured":"Lee A et al (2017) Casein kinase II phosphorylation of cyclin F at serine 621 regulates the Lys48-ubiquitylation E3 ligase activity of the SCF(cyclin F)complex. Open Biol 7(10):170058. https:\/\/doi.org\/10.1098\/rsob.170058","DOI":"10.1098\/rsob.170058"},{"issue":"2","key":"3355_CR20","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1007\/s00018-017-2632-8","volume":"75","author":"A Lee","year":"2018","unstructured":"Lee A et al (2018) Pathogenic mutation in the ALS\/FTD gene, CCNF, causes elevated Lys48-linked ubiquitylation and defective autophagy. Cell Mol Life Sci 75(2):335\u2013354. https:\/\/doi.org\/10.1007\/s00018-017-2632-8","journal-title":"Cell Mol Life Sci"},{"key":"3355_CR21","doi-asserted-by":"publisher","first-page":"59","DOI":"10.3389\/fnmol.2021.627740","volume":"14","author":"F Cheng","year":"2021","unstructured":"Cheng F et al (2021) Unbiased label-free quantitative proteomics of cells expressing amyotrophic lateral sclerosis (ALS) mutations in CCNF reveals activation of the apoptosis pathway: a workflow to screen pathogenic gene mutations. Front Mol Neurosci 14:59. https:\/\/doi.org\/10.3389\/fnmol.2021.627740","journal-title":"Front Mol Neurosci"},{"key":"3355_CR22","doi-asserted-by":"publisher","first-page":"105673","DOI":"10.1016\/J.NBD.2022.105673","volume":"167","author":"SL Rayner","year":"2022","unstructured":"Rayner SL et al (2022) TDP-43 is a ubiquitylation substrate of the SCFcyclin F complex. Neurobiol Dis 167:105673. https:\/\/doi.org\/10.1016\/J.NBD.2022.105673","journal-title":"Neurobiol Dis"},{"key":"3355_CR23","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddab073","author":"SL Rayner","year":"2021","unstructured":"Rayner SL et al (2021) ALS\/FTD-causing mutation in cyclin F causes the dysregulation of SFPQ. Hum Mol Genet. https:\/\/doi.org\/10.1093\/hmg\/ddab073","journal-title":"Hum Mol Genet"},{"issue":"14","key":"3355_CR24","doi-asserted-by":"publisher","first-page":"2616","DOI":"10.1093\/hmg\/ddx136","volume":"26","author":"AL Hogan","year":"2017","unstructured":"Hogan AL et al (2017) Expression of ALS\/FTD-linked mutant CCNF in zebrafish leads to increased cell death in the spinal cord and an aberrant motor phenotype. Hum Mol Genet 26(14):2616\u20132626. https:\/\/doi.org\/10.1093\/hmg\/ddx136","journal-title":"Hum Mol Genet"},{"key":"3355_CR25","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddz119","author":"Y Yu","year":"2019","unstructured":"Yu Y et al (2019) Pathogenic mutations in the ALS gene CCNF cause cytoplasmic mislocalization of Cyclin F and elevated VCP ATPase activity. Hum Mol Genet. https:\/\/doi.org\/10.1093\/hmg\/ddz119","journal-title":"Hum Mol Genet"},{"key":"3355_CR26","doi-asserted-by":"publisher","unstructured":"Rayner SL et al (2022) Cyclin F, neurodegeneration, and the pathogenesis of ALS\/FTD. Neuroscientist, p 107385842211201. https:\/\/doi.org\/10.1177\/10738584221120182","DOI":"10.1177\/10738584221120182"},{"issue":"4","key":"3355_CR27","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1007\/S00401-004-0821-7","volume":"107","author":"T Nakano","year":"2004","unstructured":"Nakano T, Nakaso K, Nakashima K, Ohama E (2004) Expression of ubiquitin-binding protein p62 in ubiquitin-immunoreactive intraneuronal inclusions in amyotrophic lateral sclerosis with dementia: analysis of five autopsy cases with broad clinicopathological spectrum. Acta Neuropathol 107(4):359\u2013364. https:\/\/doi.org\/10.1007\/S00401-004-0821-7","journal-title":"Acta Neuropathol"},{"issue":"2","key":"3355_CR28","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1007\/s00401-008-0402-2","volume":"116","author":"M Hiji Masanori","year":"2008","unstructured":"Hiji Masanori M, Takahashi T, Fukuba H, Yamashita H, Kohriyama T, Matsumoto M (2008) White matter lesions in the brain with frontotemporal lobar degeneration with motor neuron disease: TDP-43-immunopositive inclusions co-localize with p62, but not ubiquitin. Acta Neuropathol 116(2):183\u2013191. https:\/\/doi.org\/10.1007\/s00401-008-0402-2","journal-title":"Acta Neuropathol"},{"issue":"11","key":"3355_CR29","doi-asserted-by":"publisher","first-page":"1440","DOI":"10.1001\/archneurol.2011.250","volume":"68","author":"F Fecto","year":"2011","unstructured":"Fecto F et al (2011) SQSTM1 mutations in familial and sporadic amyotrophic lateral sclerosis. Arch Neurol 68(11):1440\u20131446. https:\/\/doi.org\/10.1001\/archneurol.2011.250","journal-title":"Arch Neurol"},{"issue":"6","key":"3355_CR30","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1002\/ana.22051","volume":"67","author":"HX Deng","year":"2010","unstructured":"Deng HX et al (2010) FUS-immunoreactive inclusions are a common feature in sporadic and non-SOD1 familial amyotrophic lateral sclerosis. Ann Neurol 67(6):739\u2013748. https:\/\/doi.org\/10.1002\/ana.22051","journal-title":"Ann Neurol"},{"issue":"3","key":"3355_CR31","doi-asserted-by":"publisher","first-page":"726.e7","DOI":"10.1016\/j.neurobiolaging.2013.09.008","volume":"35","author":"YP Chen","year":"2014","unstructured":"Chen YP et al (2014) SQSTM1 mutations in Han Chinese populations with sporadic amyotrophic lateral sclerosis. Neurobiol Aging 35(3):726.e7-726.e9. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2013.09.008","journal-title":"Neurobiol Aging"},{"issue":"4","key":"3355_CR32","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1007\/s00401-013-1090-0","volume":"125","author":"E Teyssou","year":"2013","unstructured":"Teyssou E et al (2013) Mutations in SQSTM1 encoding p62 in amyotrophic lateral sclerosis: Genetics and neuropathology. Acta Neuropathol 125(4):511\u2013522. https:\/\/doi.org\/10.1007\/s00401-013-1090-0","journal-title":"Acta Neuropathol"},{"key":"3355_CR33","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1007\/s00401-013-1150-5","volume":"3","author":"H Shimizu","year":"2013","unstructured":"Shimizu H et al (2013) Sporadic ALS with compound heterozygous mutations in the SQSTM1 gene. Acta Neuropathol 3:453\u2013459. https:\/\/doi.org\/10.1007\/s00401-013-1150-5","journal-title":"Acta Neuropathol"},{"key":"3355_CR34","doi-asserted-by":"publisher","first-page":"105653","DOI":"10.1016\/J.NBD.2022.105653","volume":"166","author":"JM Davidson","year":"2022","unstructured":"Davidson JM, Chung RS, Lee A (2022) The converging roles of sequestosome-1\/p62 in the molecular pathways of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Neurobiol Dis 166:105653. https:\/\/doi.org\/10.1016\/J.NBD.2022.105653","journal-title":"Neurobiol Dis"},{"key":"3355_CR35","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.284977","author":"A Foster","year":"2020","unstructured":"Foster A, Rea S (2020) The role of sequestosome 1\/p62 protein in amyotrophic lateral sclerosis and frontotemporal dementia pathogenesis. Neural Regen Res. https:\/\/doi.org\/10.4103\/1673-5374.284977","journal-title":"Neural Regen Res"},{"key":"3355_CR36","doi-asserted-by":"publisher","DOI":"10.1186\/s11658-016-0031-z","author":"WJ Liu","year":"2016","unstructured":"Liu WJ et al (2016) p62 links the autophagy pathway and the ubiqutin-proteasome system upon ubiquitinated protein degradation. Cell Mol Biol Lett. https:\/\/doi.org\/10.1186\/s11658-016-0031-z","journal-title":"Cell Mol Biol Lett"},{"key":"3355_CR37","doi-asserted-by":"publisher","DOI":"10.1089\/dna.2012.1915","author":"X Lin","year":"2013","unstructured":"Lin X et al (2013) Interaction domains of p62: a bridge between p62 and selective autophagy. DNA Cell Biol. https:\/\/doi.org\/10.1089\/dna.2012.1915","journal-title":"DNA Cell Biol"},{"key":"3355_CR38","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M303221200","author":"T Lamark","year":"2003","unstructured":"Lamark T et al (2003) Interaction codes within the family of mammalian Phox and Bem1p domain-containing proteins. J Biol Chem. https:\/\/doi.org\/10.1074\/jbc.M303221200","journal-title":"J Biol Chem"},{"issue":"2","key":"3355_CR39","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/j.molcel.2011.07.039","volume":"44","author":"G Matsumoto","year":"2011","unstructured":"Matsumoto G, Wada K, Okuno M, Kurosawa M, Nukina N (2011) Serine 403 phosphorylation of p62\/SQSTM1 regulates selective autophagic clearance of ubiquitinated proteins. Mol Cell 44(2):279\u2013289. https:\/\/doi.org\/10.1016\/j.molcel.2011.07.039","journal-title":"Mol Cell"},{"issue":"15","key":"3355_CR40","doi-asserted-by":"publisher","first-page":"4429","DOI":"10.1093\/hmg\/ddv179","volume":"24","author":"G Matsumoto","year":"2015","unstructured":"Matsumoto G, Shimogori T, Hattori N, Nukina N (2015) TBK1 controls autophagosomal engulfment of polyubiquitinated mitochondria through p62\/SQSTM1 phosphorylation. Hum Mol Genet 24(15):4429\u20134442. https:\/\/doi.org\/10.1093\/hmg\/ddv179","journal-title":"Hum Mol Genet"},{"key":"3355_CR41","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004987","author":"J Lim","year":"2015","unstructured":"Lim J et al (2015) Proteotoxic stress induces phosphorylation of p62\/SQSTM1 by ULK1 to regulate selective autophagic clearance of protein aggregates. PLoS Genet. https:\/\/doi.org\/10.1371\/journal.pgen.1004987","journal-title":"PLoS Genet"},{"issue":"2","key":"3355_CR42","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/j.immuni.2012.04.015","volume":"37","author":"M Pilli","year":"2012","unstructured":"Pilli M et al (2012) TBK-1 promotes autophagy-mediated antimicrobial defense by controlling autophagosome maturation. Immunity 37(2):223\u2013234. https:\/\/doi.org\/10.1016\/j.immuni.2012.04.015","journal-title":"Immunity"},{"key":"3355_CR43","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.11.005","author":"RJ Heath","year":"2016","unstructured":"Heath RJ et al (2016) RNF166 determines recruitment of adaptor proteins during antibacterial autophagy. Cell Rep. https:\/\/doi.org\/10.1016\/j.celrep.2016.11.005","journal-title":"Cell Rep"},{"issue":"5","key":"3355_CR44","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1016\/J.MOLCEL.2016.02.007","volume":"61","author":"JA Pan","year":"2016","unstructured":"Pan JA et al (2016) TRIM21 ubiquitylates SQSTM1\/p62 and suppresses protein sequestration to regulate redox homeostasis. Mol Cell 61(5):720. https:\/\/doi.org\/10.1016\/J.MOLCEL.2016.02.007","journal-title":"Mol Cell"},{"issue":"1","key":"3355_CR45","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1016\/j.celrep.2017.03.030","volume":"19","author":"YJ Lee","year":"2017","unstructured":"Lee YJ, Chou TF, Pittman SK, Keith AL, Razani B, Weihl CC (2017) Keap1\/Cullin3 modulates p62\/SQSTM1 activity via UBA domain ubiquitination. Cell Rep 19(1):188\u2013202. https:\/\/doi.org\/10.1016\/j.celrep.2017.03.030","journal-title":"Cell Rep"},{"key":"3355_CR46","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.207068","author":"Q Lin","year":"2017","unstructured":"Lin Q et al (2017) The HECT E3 ubiquitin ligase NEDD4 interacts with and ubiquitylates SQSTM1 for inclusion body autophagy. J Cell Sci. https:\/\/doi.org\/10.1242\/jcs.207068","journal-title":"J Cell Sci"},{"key":"3355_CR47","doi-asserted-by":"publisher","first-page":"5800","DOI":"10.1038\/ncomms6800","volume":"6","author":"DK Klein","year":"2015","unstructured":"Klein DK et al (2015) Cyclin F suppresses B-Myb activity to promote cell cycle checkpoint control. Nat Commun 6:5800. https:\/\/doi.org\/10.1038\/ncomms6800","journal-title":"Nat Commun"},{"key":"3355_CR48","doi-asserted-by":"publisher","DOI":"10.1002\/cpim.58","author":"MS Alam","year":"2018","unstructured":"Alam MS (2018) Proximity ligation assay (PLA). Curr Protoc Immunol. https:\/\/doi.org\/10.1002\/cpim.58","journal-title":"Curr Protoc Immunol"},{"key":"3355_CR49","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2017.40","author":"H Peng","year":"2017","unstructured":"Peng H et al (2017) Ubiquitylation of p62\/sequestosome1 activates its autophagy receptor function and controls selective autophagy upon ubiquitin stress. Cell Res. https:\/\/doi.org\/10.1038\/cr.2017.40","journal-title":"Cell Res"},{"key":"3355_CR50","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku1267","volume-title":"PhosphoSitePlus, 2014: Mutations","author":"PV Hornbeck","year":"2015","unstructured":"Hornbeck PV, Zhang B, Murray B, Kornhauser JM, Latham V, Skrzypek E (2015) PhosphoSitePlus, 2014: Mutations. Nucleic Acids Res, PTMs and recalibrations. https:\/\/doi.org\/10.1093\/nar\/gku1267"},{"key":"3355_CR51","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2019.101530","author":"M Bax","year":"2019","unstructured":"Bax M et al (2019) Generation and characterization of a human induced pluripotent stem cell line UOWi005-A from dermal fibroblasts derived from a CCNFS621G familial amyotrophic lateral sclerosis patient using mRNA reprogramming. Stem Cell Res. https:\/\/doi.org\/10.1016\/j.scr.2019.101530","journal-title":"Stem Cell Res"},{"key":"3355_CR52","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.214304","author":"A Danieli","year":"2018","unstructured":"Danieli A, Martens S (2018) P62 - Mediated phase separation at the intersection of the ubiquitin-Proteasome system and autophagy. J Cell Sci. https:\/\/doi.org\/10.1242\/jcs.214304","journal-title":"J Cell Sci"},{"key":"3355_CR53","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2018.00128","author":"NM Kocaturk","year":"2018","unstructured":"Kocaturk NM, Gozuacik D (2018) Crosstalk between mammalian autophagy and the ubiquitin-proteasome system. Front Cell Dev Biol. https:\/\/doi.org\/10.3389\/fcell.2018.00128","journal-title":"Front Cell Dev Biol"},{"key":"3355_CR54","doi-asserted-by":"publisher","DOI":"10.1126\/science.aax3769","author":"C Pohl","year":"2019","unstructured":"Pohl C, Dikic I (2019) Cellular quality control by the ubiquitin-proteasome system and autophagy. Science. https:\/\/doi.org\/10.1126\/science.aax3769","journal-title":"Science"},{"issue":"3","key":"3355_CR55","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.tcb.2012.10.011","volume":"23","author":"V D\u2019Angiolella","year":"2013","unstructured":"D\u2019Angiolella V, Esencay M, Pagano M (2013) A cyclin without cyclin-dependent kinases: cyclin F controls genome stability through ubiquitin-mediated proteolysis. Trends Cell Biol 23(3):135\u2013140. https:\/\/doi.org\/10.1016\/j.tcb.2012.10.011","journal-title":"Trends Cell Biol"},{"issue":"5","key":"3355_CR56","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1038\/cr.2017.40","volume":"27","author":"H Peng","year":"2017","unstructured":"Peng H et al (2017) Ubiquitylation of p62\/sequestosome1 activates its autophagy receptor function and controls selective autophagy upon ubiquitin stress. Cell Res 27(5):657\u2013674. https:\/\/doi.org\/10.1038\/cr.2017.40","journal-title":"Cell Res"},{"issue":"7","key":"3355_CR57","doi-asserted-by":"publisher","first-page":"e635","DOI":"10.1212\/WNL.0000000000005996","volume":"91","author":"A Chi\u00f2","year":"2018","unstructured":"Chi\u00f2 A et al (2018) The multistep hypothesis of ALS revisited. Neurology 91(7):e635\u2013e642. https:\/\/doi.org\/10.1212\/WNL.0000000000005996","journal-title":"Neurology"},{"issue":"11","key":"3355_CR58","doi-asserted-by":"publisher","first-page":"1108","DOI":"10.1016\/S1474-4422(14)70219-4","volume":"13","author":"A Al-Chalabi","year":"2014","unstructured":"Al-Chalabi A et al (2014) Analysis of amyotrophic lateral sclerosis as a multistep process: a population-based modelling study. Lancet Neurol 13(11):1108\u20131113. https:\/\/doi.org\/10.1016\/S1474-4422(14)70219-4","journal-title":"Lancet Neurol"},{"issue":"7\u20138","key":"3355_CR59","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1080\/21678421.2018.1556697","volume":"20","author":"S Vucic","year":"2019","unstructured":"Vucic S, Westeneng HJ, Al-Chalabi A, van den Berg LH, Talman P, Kiernan MC (2019) Amyotrophic lateral sclerosis as a multi-step process: an Australia population study. Amyotroph Lateral Scler Frontotemporal Degener 20(7\u20138):532\u2013537. https:\/\/doi.org\/10.1080\/21678421.2018.1556697","journal-title":"Amyotroph Lateral Scler Frontotemporal Degener"},{"key":"3355_CR60","doi-asserted-by":"publisher","DOI":"10.1007\/s13238-015-0230-9","author":"P Song","year":"2016","unstructured":"Song P et al (2016) Parkin promotes proteasomal degradation of p62: implication of selective vulnerability of neuronal cells in the pathogenesis of Parkinson\u2019s disease. Protein Cell. https:\/\/doi.org\/10.1007\/s13238-015-0230-9","journal-title":"Protein Cell"},{"key":"3355_CR61","doi-asserted-by":"publisher","unstructured":"Siebert A, Gattringer V, Weishaupt JH, Behrends C (2022) ALS-linked loss of Cyclin-F function affects HSP90. Life Sci Alliance 5(12):e202101359. https:\/\/doi.org\/10.26508\/lsa.202101359","DOI":"10.26508\/lsa.202101359"},{"issue":"6","key":"3355_CR62","doi-asserted-by":"publisher","first-page":"4033","DOI":"10.1074\/jbc.M111.280065","volume":"287","author":"J Lee","year":"2012","unstructured":"Lee J et al (2012) Autophagy suppresses interleukin-1\u03b2 (IL-1\u03b2) signaling by activation of p62 degradation via lysosomal and proteasomal pathways. J Biol Chem 287(6):4033\u20134040. https:\/\/doi.org\/10.1074\/jbc.M111.280065","journal-title":"J Biol Chem"},{"key":"3355_CR63","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2016.02.007","author":"JA Pan","year":"2016","unstructured":"Pan JA et al (2016) TRIM21 ubiquitylates SQSTM1\/p62 and suppresses protein sequestration to regulate redox homeostasis. Mol Cell. https:\/\/doi.org\/10.1016\/j.molcel.2016.02.007","journal-title":"Mol Cell"},{"key":"3355_CR64","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1016\/j.molcel.2016.03.015","volume":"61","author":"JA Pan","year":"2016","unstructured":"Pan JA et al (2016) Corrections to \"TRIM21 ubiquitylates SQSTM1\/p62 and suppresses protein sequestration to regulate redox homeostasis. Mol Cell 61:720\u201333. https:\/\/doi.org\/10.1016\/j.molcel.2016.03.015","journal-title":"Mol Cell"},{"key":"3355_CR65","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2020.03.002","author":"JJ Yerbury","year":"2020","unstructured":"Yerbury JJ, Farrawell NE, McAlary L (2020) Proteome homeostasis dysfunction: a unifying principle in ALS pathogenesis. Trends Neurosci. https:\/\/doi.org\/10.1016\/j.tins.2020.03.002","journal-title":"Trends Neurosci"},{"key":"3355_CR66","doi-asserted-by":"crossref","unstructured":"Saitoh Y, Nagai Y (2017) Commentary Open Access Commentary: p62 plays a protective role in the autophagic degradation of polyglutamine protein oligomers in polyglutamine disease model flies. Dis Res Treat 2(3):7\u201310. [Online]. Available: www.rarediseasesjournal.com. Accessed 19 May 2022","DOI":"10.29245\/2572-9411\/2017\/3.1106"},{"issue":"1","key":"3355_CR67","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/J.TCB.2015.08.010","volume":"26","author":"A Khaminets","year":"2016","unstructured":"Khaminets A, Behl C, Dikic I (2016) Ubiquitin-dependent and independent signals in selective autophagy. Trends Cell Biol 26(1):6\u201316. https:\/\/doi.org\/10.1016\/J.TCB.2015.08.010","journal-title":"Trends Cell Biol"},{"key":"3355_CR68","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200507002","author":"G Bj\u00f8rk\u00f8y","year":"2005","unstructured":"Bj\u00f8rk\u00f8y G et al (2005) p62\/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death. J Cell Biol. https:\/\/doi.org\/10.1083\/jcb.200507002","journal-title":"J Cell Biol"},{"issue":"4","key":"3355_CR69","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/s41422-018-0017-7","volume":"28","author":"D Sun","year":"2018","unstructured":"Sun D, Wu R, Zheng J, Li P, Yu L (2018) Polyubiquitin chain-induced p62 phase separation drives autophagic cargo segregation. Cell Res 28(4):405\u2013415. https:\/\/doi.org\/10.1038\/s41422-018-0017-7","journal-title":"Cell Res"},{"key":"3355_CR70","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M608787200","author":"J Gal","year":"2007","unstructured":"Gal J, Str\u00f6m AL, Kilty R, Zhang F, Zhu H (2007) p62 accumulates and enhances aggregate formation in model systems of familial amyotrophic lateral sclerosis. J Biol Chem. https:\/\/doi.org\/10.1074\/jbc.M608787200","journal-title":"J Biol Chem"},{"issue":"22","key":"3355_CR71","doi-asserted-by":"publisher","first-page":"5029","DOI":"10.1016\/J.FEBSLET.2005.08.010","volume":"579","author":"MG Paine","year":"2005","unstructured":"Paine MG, Babu JR, Seibenhener ML, Wooten MW (2005) Evidence for p62 aggregate formation: role in cell survival. FEBS Lett 579(22):5029\u20135034. https:\/\/doi.org\/10.1016\/J.FEBSLET.2005.08.010","journal-title":"FEBS Lett"},{"issue":"1","key":"3355_CR72","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/S1097-2765(03)00246-6\/ATTACHMENT\/670E876D-2E33-454D-BAB1-6F62D4D6B450\/MMC5.JPG","volume":"12","author":"MI Wilson","year":"2003","unstructured":"Wilson MI, Gill DJ, Perisic O, Quinn MT, Williams RL (2003) PB1 domain-mediated heterodimerization in NADPH oxidase and signaling complexes of atypical protein kinase C with Par6 and p62. Mol Cell 12(1):39\u201350. https:\/\/doi.org\/10.1016\/S1097-2765(03)00246-6\/ATTACHMENT\/670E876D-2E33-454D-BAB1-6F62D4D6B450\/MMC5.JPG","journal-title":"Mol Cell"},{"issue":"1","key":"3355_CR73","doi-asserted-by":"publisher","first-page":"11474","DOI":"10.1038\/s41598-021-90822-2","volume":"11","author":"AD Foster","year":"2021","unstructured":"Foster AD et al (2021) p62 overexpression induces TDP-43 cytoplasmic mislocalisation, aggregation and cleavage and neuronal death. Sci Rep 11(1):11474. https:\/\/doi.org\/10.1038\/s41598-021-90822-2","journal-title":"Sci Rep"},{"issue":"8","key":"3355_CR74","doi-asserted-by":"publisher","first-page":"6521","DOI":"10.1074\/JBC.M110.172288","volume":"286","author":"JA Young","year":"2011","unstructured":"Young JA et al (2011) Fas-associated death domain (FADD) and the E3 ubiquitin-protein ligase TRIM21 interact to negatively regulate virus-induced interferon production. J Biol Chem 286(8):6521\u20136531. https:\/\/doi.org\/10.1074\/JBC.M110.172288","journal-title":"J Biol Chem"},{"key":"3355_CR75","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.mcn.2016.03.010","volume":"74","author":"JM Davidson","year":"2016","unstructured":"Davidson JM, Wong CT, Rai-Bhogal R, Li H, Crawford DA (2016) Prostaglandin E2 elevates calcium in differentiated neuroectodermal stem cells. Mol Cell Neurosci 74:71\u201377. https:\/\/doi.org\/10.1016\/j.mcn.2016.03.010","journal-title":"Mol Cell Neurosci"},{"key":"3355_CR76","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/j.bbrep.2016.06.001","volume":"7","author":"JM Davidson","year":"2016","unstructured":"Davidson JM, Wong CT, Li H, Crawford DA (2016) Prostaglandin E2 facilitates subcellular translocation of the EP4 receptor in neuroectodermal NE-4C stem cells. Biochem Biophys Rep 7:173\u2013179. https:\/\/doi.org\/10.1016\/j.bbrep.2016.06.001","journal-title":"Biochem Biophys Rep"},{"key":"3355_CR77","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2019-321790","author":"EP McCann","year":"2019","unstructured":"McCann EP et al (2019) Genetic and immunopathological analysis of CHCHD10 in Australian amyotrophic lateral sclerosis and frontotemporal dementia and transgenic TDP-43 mice. J Neurol Neurosurg Psychiatry. https:\/\/doi.org\/10.1136\/jnnp-2019-321790","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"7","key":"3355_CR78","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/nmeth.2019","volume":"9","author":"J Schindelin","year":"2012","unstructured":"Schindelin J et al (2012) Fiji: an open-source platform for biological-image analysis. Nat Methods 9(7):676\u2013682. https:\/\/doi.org\/10.1038\/nmeth.2019","journal-title":"Nat Methods"},{"issue":"3","key":"3355_CR79","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1111\/j.1365-2818.2006.01706.x","volume":"224","author":"S Bolte","year":"2006","unstructured":"Bolte S, Cordeli\u00e8res FP (2006) A guided tour into subcellular colocalization analysis in light microscopy. J Microsc 224(3):213\u2013232. https:\/\/doi.org\/10.1111\/j.1365-2818.2006.01706.x","journal-title":"J Microsc"}],"container-title":["Molecular Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-023-03355-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12035-023-03355-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-023-03355-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T09:34:00Z","timestamp":1691660040000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12035-023-03355-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,27]]},"references-count":79,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2023,9]]}},"alternative-id":["3355"],"URL":"https:\/\/doi.org\/10.1007\/s12035-023-03355-2","relation":{},"ISSN":["0893-7648","1559-1182"],"issn-type":[{"value":"0893-7648","type":"print"},{"value":"1559-1182","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,27]]},"assertion":[{"value":"7 August 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 April 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 May 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The control cases and the CCNF S621G patient tissues have been provided with written consent through regional brain donor programs from the NSW Brain Tissue Resource Centre, the Sydney Brain Bank, Australia, respectively. The CCNF S195R patient was recruited through brain donor program at the CIEN Tissue Bank in Spain. In compliance with the brain bank's protocols, an informed consent for brain donation was obtained for both Brain Banks. Patient fibroblasts were obtained from Macquarie University Neurodegenerative Diseases Biobank. The research conducted in this study was approved by Macquarie Human Research Ethics Committee, 5201600387. Patient fibroblasts were reprogrammed into induced pluripotent stem cells and characterized as pluripotent [] with approval from the University of Wollongong Human Research Ethics Committee HE13\/272.Post-mortem brain tissue for a patient was also obtained from a brain donor to the CIEN Tissue Bank. In compliance with the brain bank's protocols, an informed consent for brain donation was obtained intra vitam. The CIEN Tissue Bank is a brain bank registered and authorized as a biobank by the Spanish local Health and Biomedical Research authorities. Accordingly, the CIEN Tissue Bank complies with Spanish and European regulations concerning the use of human biological samples and personal data protection in biomedical research.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"N\/A.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}},{"value":"N\/A.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publication"}},{"value":"The authors declare that they have no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interests"}}]}}