{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:03:27Z","timestamp":1791407007210,"version":"4.3.3"},"reference-count":77,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T00:00:00Z","timestamp":1734652800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004040","name":"KU Leuven","doi-asserted-by":"publisher","award":["C1-C14-17-107"],"award-info":[{"award-number":["C1-C14-17-107"]}],"id":[{"id":"10.13039\/501100004040","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Opening the Future Fund"},{"name":"Agency for Innovation by Science and Technology","award":["150031"],"award-info":[{"award-number":["150031"]}]},{"name":"Agency for Innovation by Science and Technology","award":["135043"],"award-info":[{"award-number":["135043"]}]},{"name":"ALS Liga Belgi\u00eb"},{"name":"National Lottery of Belgium"},{"name":"European E-Rare-3 project INTEGRALS"},{"name":"European E-Rare-3 project MAXOMOD"},{"DOI":"10.13039\/501100014076","name":"Stichting ALS Nederland","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014076","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Vlaanderen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010663","name":"European Research Council","doi-asserted-by":"publisher","award":["772376"],"award-info":[{"award-number":["772376"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Progressive loss of motor neurons is the hallmark of the neurodegenerative disease amyotrophic lateral sclerosis (ALS), but the underlying disease mechanisms remain incompletely understood. In this study, we investigate the effects of C21ORF2 mutations, a gene recently linked to ALS, and find that primary cilia are dysfunctional. Human patient-derived mutant C21ORF2 motor neurons have a reduced ciliary frequency and length.<\/jats:p>\n                  <jats:p>We report that C21ORF2 is located at the basal body of the primary cilium, and mutations associated with ALS alter this localization. Furthermore, we show that a reduction of C21ORF2 levels in cell lines and motor neurons is sufficient to cause fewer primary cilia and reduced cilial length. This ciliary dysfunction leads to defective downstream sonic hedgehog signalling and reduces the expression of cellular retinoic acid binding protein 1 (CRABP1), a protein involved in motor neuron maintenance and survival.<\/jats:p>\n                  <jats:p>In a compartmentalized co-culture system of motor neurons and muscle cells, these ciliary defects were associated with a reduced ability of neuromuscular junction formation. Interestingly, these cilia defects are seemingly not restricted to C21ORF2 ALS, as we also observed perturbed primary cilia in cultured motor neurons and post-mortem motor cortex from patients with the most common genetic subtype of ALS caused by repeat expansions in the C9ORF72 gene. Finally, overexpression of C21ORF2 in mutant C21ORF2 motor neurons rescued the ciliary frequency and length, CRAPBP1 expression and neuromuscular junction formation, confirming the importance of primary cilia for motor neuron function.<\/jats:p>\n                  <jats:p>These results point towards primary cilia dysfunction contributing to motor neuron degeneration in ALS and open new avenues for further research and interventions for this as yet untreatable disease.<\/jats:p>","DOI":"10.1093\/brain\/awae331","type":"journal-article","created":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T11:49:57Z","timestamp":1728992997000},"page":"803-816","source":"Crossref","is-referenced-by-count":18,"title":["<i>C21ORF2<\/i>\n                    mutations point towards primary cilia dysfunction in amyotrophic lateral sclerosis"],"prefix":"10.1093","volume":"148","author":[{"given":"Mathias","family":"De Decker","sequence":"first","affiliation":[{"name":"Department of Neurosciences, Laboratory of Neurobiology and Leuven Brain Institute (LBI), KU Leuven\u2014University of Leuven , 3000 Leuven ,","place":["Belgium"]},{"name":"VIB, Center for Brain & Disease Research , 3000 Leuven ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavol","family":"Zelina","sequence":"additional","affiliation":[{"name":"Department of Translational Neuroscience, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, 3584 CG Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas G","family":"Moens","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Laboratory of Neurobiology and Leuven Brain Institute (LBI), KU Leuven\u2014University of Leuven , 3000 Leuven ,","place":["Belgium"]},{"name":"VIB, Center for Brain & Disease Research , 3000 Leuven ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jimmy","family":"Beckers","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Laboratory of Neurobiology and Leuven Brain Institute (LBI), KU Leuven\u2014University of Leuven , 3000 Leuven ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matilde","family":"Contardo","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Laboratory of Neurobiology and Leuven Brain Institute (LBI), KU Leuven\u2014University of Leuven , 3000 Leuven ,","place":["Belgium"]},{"name":"VIB, Center for Brain & Disease Research , 3000 Leuven ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarina Stoklund","family":"Dittlau","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Laboratory of Neurobiology and Leuven Brain Institute (LBI), KU Leuven\u2014University of Leuven , 3000 Leuven ,","place":["Belgium"]},{"name":"VIB, Center for Brain & Disease Research , 3000 Leuven ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelien","family":"Van Schoor","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Laboratory of Neurobiology and Leuven Brain Institute (LBI), KU Leuven\u2014University of Leuven , 3000 Leuven ,","place":["Belgium"]},{"name":"VIB, Center for Brain & Disease Research , 3000 Leuven ,","place":["Belgium"]},{"name":"Laboratory of Neuropathology, Department of Imaging and Pathology, Leuven Brain Institute (LBI), KU Leuven (University of Leuven) , 3000 Leuven ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicja","family":"Ronisz","sequence":"additional","affiliation":[{"name":"Laboratory of Neuropathology, Department of Imaging and Pathology, Leuven Brain Institute (LBI), KU Leuven (University of Leuven) , 3000 Leuven ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristel","family":"Eggermont","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Laboratory of Neurobiology and Leuven Brain Institute (LBI), KU Leuven\u2014University of Leuven , 3000 Leuven ,","place":["Belgium"]},{"name":"VIB, Center for Brain & Disease Research , 3000 Leuven ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthieu","family":"Moisse","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Laboratory of Neurobiology and Leuven Brain Institute (LBI), KU Leuven\u2014University of Leuven , 3000 Leuven ,","place":["Belgium"]},{"name":"VIB, Center for Brain & Disease Research , 3000 Leuven ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siddharthan","family":"Chandran","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute at the University of Edinburgh , Edinburgh EH16 4SB ,","place":["UK"]},{"name":"Centre for Clinical Brain Sciences, University of Edinburgh , Edinburgh EH16 4SB ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan H","family":"Veldink","sequence":"additional","affiliation":[{"name":"Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University , 3584 CX Utrecht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dietmar Rudolf","family":"Thal","sequence":"additional","affiliation":[{"name":"Laboratory of Neuropathology, Department of Imaging and Pathology, Leuven Brain Institute (LBI), KU Leuven (University of Leuven) , 3000 Leuven ,","place":["Belgium"]},{"name":"Department of Pathology, University Hospitals Leuven , 3000 Leuven ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludo","family":"Van Den Bosch","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Laboratory of Neurobiology and Leuven Brain Institute (LBI), KU Leuven\u2014University of Leuven , 3000 Leuven ,","place":["Belgium"]},{"name":"VIB, Center for Brain & Disease Research , 3000 Leuven ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R Jeroen","family":"Pasterkamp","sequence":"additional","affiliation":[{"name":"Department of Translational Neuroscience, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, 3584 CG Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4010-2357","authenticated-orcid":false,"given":"Philip","family":"Van Damme","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Laboratory of Neurobiology and Leuven Brain Institute (LBI), KU Leuven\u2014University of Leuven , 3000 Leuven ,","place":["Belgium"]},{"name":"Department of Neurology, University Hospitals Leuven , 3000 Leuven ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,12,20]]},"reference":[{"key":"2025030619392966400_awae331-B1","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1056\/NEJMra1603471","article-title":"Amyotrophic lateral sclerosis","volume":"377","author":"Brown","year":"2017","journal-title":"N Engl J Med."},{"key":"2025030619392966400_awae331-B2","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.1111\/ene.14393","article-title":"Amyotrophic lateral sclerosis: A clinical review","volume":"27","author":"Masrori","year":"2020","journal-title":"Eur J Neurol."},{"key":"2025030619392966400_awae331-B3","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1038\/nrneurol.2014.184","article-title":"The phenotypic variability of amyotrophic lateral sclerosis","volume":"10","author":"Swinnen","year":"2014","journal-title":"Nat Rev Neurol."},{"key":"2025030619392966400_awae331-B4","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1056\/NEJM199403033300901","article-title":"A controlled trial of riluzole in amyotrophic lateral sclerosis","volume":"330","author":"Bensimon","year":"1994","journal-title":"N Engl J Med."},{"key":"2025030619392966400_awae331-B5","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/S1474-4422(17)30115-1","article-title":"Safety and efficacy of edaravone in well defined patients with amyotrophic lateral sclerosis: A randomised, double-blind, placebo-controlled trial","volume":"16","author":"Abe","year":"2017","journal-title":"Lancet Neurol."},{"key":"2025030619392966400_awae331-B6","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1056\/NEJMoa1916945","article-title":"Trial of sodium phenylbutyrate-taurursodiol for amyotrophic lateral sclerosis","volume":"383","author":"Paganoni","year":"2020","journal-title":"N Engl J Med."},{"key":"2025030619392966400_awae331-B7","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1056\/NEJMoa2204705","article-title":"Trial of antisense oligonucleotide Tofersen for SOD1 ALS","volume":"387","author":"Miller","year":"2022","journal-title":"N Engl J Med."},{"key":"2025030619392966400_awae331-B8","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1136\/jnnp.2010.224501","article-title":"Rate of familial amyotrophic lateral sclerosis: A systematic review and meta-analysis","volume":"82","author":"Byrne","year":"2011","journal-title":"J Neurol Neurosurg Psychiatry."},{"key":"2025030619392966400_awae331-B9","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.tig.2018.03.001","article-title":"ALS genes in the genomic era and their implications for FTD","volume":"34","author":"Nguyen","year":"2018","journal-title":"Trends Genet."},{"key":"2025030619392966400_awae331-B10","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1136\/jnnp-2016-315018","article-title":"Genetic epidemiology of amyotrophic lateral sclerosis: A systematic review and meta-analysis","volume":"88","author":"Zou","year":"2017","journal-title":"J Neurol Neurosurg Psychiatry."},{"key":"2025030619392966400_awae331-B11","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1136\/jmedgenet-2013-101795","article-title":"Delineating the genetic heterogeneity of ALS using targeted high-throughput sequencing","volume":"50","author":"Kenna","year":"2013","journal-title":"J Med Genet."},{"key":"2025030619392966400_awae331-B12","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1212\/WNL.0000000000004109","article-title":"The evolving genetic risk for sporadic ALS","volume":"89","author":"Gibson","year":"2017","journal-title":"Neurology"},{"key":"2025030619392966400_awae331-B13","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1242\/dmm.029058","article-title":"Modelling amyotrophic lateral sclerosis: Progress and possibilities","volume":"10","author":"Van Damme","year":"2017","journal-title":"Dis Model Mech."},{"key":"2025030619392966400_awae331-B14","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1038\/ng.3622","article-title":"Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis","volume":"48","author":"van Rheenen","year":"2016","journal-title":"Nat Genet."},{"key":"2025030619392966400_awae331-B15","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1080\/07391102.2018.1429313","article-title":"Prediction of structural consequences for disease causing variants in C21orf2 protein using computational approaches","volume":"37","author":"Iyer","year":"2019","journal-title":"J Biomol Struct Dyn."},{"key":"2025030619392966400_awae331-B16","doi-asserted-by":"crossref","first-page":"e0150555","DOI":"10.1371\/journal.pone.0150555","article-title":"Axial spondylometaphyseal dysplasia is caused by C21orf2 mutations","volume":"11","author":"Wang","year":"2016","journal-title":"PLoS One"},{"key":"2025030619392966400_awae331-B17","doi-asserted-by":"crossref","first-page":"1698","DOI":"10.1002\/ajmg.a.38215","article-title":"Homozygous variant in C21orf2 in a case of Jeune syndrome with severe thoracic involvement: Extending the phenotypic spectrum","volume":"173","author":"McInerney-Leo","year":"2017","journal-title":"Am J Med Genet A."},{"key":"2025030619392966400_awae331-B18","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1136\/bjophthalmol-2015-307277","article-title":"C21orf2 is mutated in recessive early-onset retinal dystrophy with macular staphyloma and encodes a protein that localises to the photoreceptor primary cilium","volume":"99","author":"Khan","year":"2015","journal-title":"Br J Ophthalmol"},{"key":"2025030619392966400_awae331-B19","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1006\/geno.1997.5066","article-title":"Characterization of a novel gene, C21orf2, on human chromosome 21q22.3 and its exclusion as the APECED gene by mutation analysis","volume":"47","author":"Scott","year":"1998","journal-title":"Genomics"},{"key":"2025030619392966400_awae331-B20","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/978-3-7091-6721-2_10","volume-title":"Advances in down syndrome research","author":"Shim","year":"2003"},{"key":"2025030619392966400_awae331-B21","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/1741-7007-9-54","article-title":"Identification and characterization of a set of conserved and new regulators of cytoskeletal organization, cell morphology and migration","volume":"9","author":"Bai","year":"2011","journal-title":"BMC Biol."},{"key":"2025030619392966400_awae331-B22","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1093\/abbs\/gmv076","article-title":"The NEK1 interactor, C21ORF2, is required for efficient DNA damage repair","volume":"47","author":"Fang","year":"2015","journal-title":"Acta Biochim Biophys Sin (Shanghai)."},{"key":"2025030619392966400_awae331-B23","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1038\/ng.3626","article-title":"NEK1 variants confer susceptibility to amyotrophic lateral sclerosis","volume":"48","author":"Kenna","year":"2016","journal-title":"Nat Genet."},{"key":"2025030619392966400_awae331-B24","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1038\/ncb3201","article-title":"An siRNA-based functional genomics screen for the identification of regulators of ciliogenesis and ciliopathy genes","volume":"17","author":"Wheway","year":"2015","journal-title":"Nat Cell Biol."},{"key":"2025030619392966400_awae331-B25","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1091\/mbc.e10-07-0596","article-title":"Functional characterization of putative cilia genes by high-content analysis","volume":"22","author":"Lai","year":"2011","journal-title":"Mol Biol Cell."},{"key":"2025030619392966400_awae331-B26","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/nature02061","article-title":"Hedgehog signalling in the mouse requires intraflagellar transport proteins","volume":"426","author":"Huangfu","year":"2003","journal-title":"Nature"},{"key":"2025030619392966400_awae331-B27","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/1471-2202-12-71","article-title":"Adenylyl cyclase type 3, a marker of primary cilia, is reduced in primary cell culture and in lumbar spinal cord in situ in G93A SOD1 mice","volume":"12","author":"Ma","year":"2011","journal-title":"BMC Neurosci."},{"key":"2025030619392966400_awae331-B28","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1136\/jnnp-2019-321279","article-title":"Retinitis pigmentosa prior to familial ALS caused by a homozygous cilia and flagella-associated protein 410 mutation","volume":"91","author":"Kurashige","year":"2020","journal-title":"J Neurol Neurosurg Psychiatry."},{"key":"2025030619392966400_awae331-B29","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1016\/0896-6273(94)90437-5","article-title":"Genetic dissection of mechanosensory transduction: Mechanoreception-defective mutations of drosophila","volume":"12","author":"Kernan","year":"1994","journal-title":"Neuron"},{"key":"2025030619392966400_awae331-B30","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1016\/j.cell.2006.05.025","article-title":"Flies without centrioles","volume":"125","author":"Basto","year":"2006","journal-title":"Cell"},{"key":"2025030619392966400_awae331-B31","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1083\/jcb.200402130","article-title":"The Drosophila pericentrin-like protein is essential for cilia\/flagella function, but appears to be dispensable for mitosis","volume":"165","author":"Martinez-Campos","year":"2004","journal-title":"J Cell Biol."},{"key":"2025030619392966400_awae331-B32","doi-asserted-by":"crossref","first-page":"3411","DOI":"10.1242\/dev.01229","article-title":"Mechanosensory-defective, male-sterile unc mutants identify a novel basal body protein required for ciliogenesis in Drosophila","volume":"131","author":"Baker","year":"2004","journal-title":"Development"},{"key":"2025030619392966400_awae331-B33","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s13630-016-0041-5","article-title":"Drosophila melanogaster as a model for basal body research","volume":"5","author":"Jana","year":"2016","journal-title":"Cilia"},{"key":"2025030619392966400_awae331-B34","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1080\/21678421.2019.1606244","article-title":"The project MinE databrowser: Bringing large-scale whole-genome sequencing in ALS to researchers and the public","volume":"20","author":"van der Spek","year":"2019","journal-title":"Amyotroph Lateral Scler Frontotemporal Degener."},{"key":"2025030619392966400_awae331-B35","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1038\/ng.2892","article-title":"A general framework for estimating the relative pathogenicity of human genetic variants","volume":"46","author":"Kircher","year":"2014","journal-title":"Nat Genet."},{"key":"2025030619392966400_awae331-B36","doi-asserted-by":"crossref","first-page":"108","DOI":"10.2174\/0929866526666181208170027","article-title":"Leucine rich repeat proteins: Sequences, mutations, structures and diseases","volume":"26","author":"Matsushima","year":"2019","journal-title":"Protein Pept Lett"},{"key":"2025030619392966400_awae331-B37","doi-asserted-by":"crossref","first-page":"3796","DOI":"10.1093\/hmg\/ddn277","article-title":"CEP290 interacts with the centriolar satellite component PCM-1 and is required for Rab8 localization to the primary cilium","volume":"17","author":"Kim","year":"2008","journal-title":"Hum Mol Genet."},{"key":"2025030619392966400_awae331-B38","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1038\/nrm952","article-title":"Intraflagellar transport","volume":"3","author":"Rosenbaum","year":"2002","journal-title":"Nat Rev Mol Cell Biol."},{"key":"2025030619392966400_awae331-B39","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1038\/nrm.2017.60","article-title":"Genes and molecular pathways underpinning ciliopathies","volume":"18","author":"Reiter","year":"2017","journal-title":"Nat Rev Mol Cell Biol."},{"key":"2025030619392966400_awae331-B40","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/2046-2530-2-10","article-title":"Intraflagellar transport complex structure and cargo interactions","volume":"2","author":"Bhogaraju","year":"2013","journal-title":"Cilia"},{"key":"2025030619392966400_awae331-B41","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/ng.832","article-title":"Complex interactions between genes controlling trafficking in primary cilia","volume":"43","author":"Ocbina","year":"2011","journal-title":"Nat Genet."},{"key":"2025030619392966400_awae331-B42","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1038\/ng.105","article-title":"THM1 negatively modulates mouse sonic hedgehog signal transduction and affects retrograde intraflagellar transport in cilia","volume":"40","author":"Tran","year":"2008","journal-title":"Nat Genet."},{"key":"2025030619392966400_awae331-B43","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.devcel.2014.09.004","article-title":"The intraflagellar transport protein IFT27 promotes BBSome exit from cilia through the GTPase ARL6\/BBS3","volume":"31","author":"Liew","year":"2014","journal-title":"Dev Cell."},{"key":"2025030619392966400_awae331-B44","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.devcel.2014.09.011","article-title":"IFT27 links the BBSome to IFT for maintenance of the ciliary signaling compartment","volume":"31","author":"Eguether","year":"2014","journal-title":"Dev Cell."},{"key":"2025030619392966400_awae331-B45","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1126\/science.1139740","article-title":"Patched1 regulates hedgehog signaling at the primary cilium","volume":"317","author":"Rohatgi","year":"2007","journal-title":"Science"},{"key":"2025030619392966400_awae331-B46","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1038\/nature04117","article-title":"Vertebrate smoothened functions at the primary cilium","volume":"437","author":"Corbit","year":"2005","journal-title":"Nature"},{"key":"2025030619392966400_awae331-B47","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1038\/nrm3598","article-title":"The mechanisms of Hedgehog signalling and its roles in development and disease","volume":"14","author":"Briscoe","year":"2013","journal-title":"Nat Rev Mol Cell Biol."},{"key":"2025030619392966400_awae331-B48","doi-asserted-by":"crossref","first-page":"2423","DOI":"10.3390\/ijms19082423","article-title":"Emerging roles of sonic hedgehog in adult neurological diseases: Neurogenesis and beyond","volume":"19","author":"Chen","year":"2018","journal-title":"Int J Mol Sci."},{"key":"2025030619392966400_awae331-B49","doi-asserted-by":"crossref","first-page":"711710","DOI":"10.3389\/fmolb.2021.711710","article-title":"The role of sonic hedgehog pathway in the development of the central nervous system and aging-related neurodegenerative diseases","volume":"8","author":"Yang","year":"2021","journal-title":"Front Mol Biosci."},{"key":"2025030619392966400_awae331-B50","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1083\/jcb.201110049","article-title":"The IFT-A complex regulates Shh signaling through cilia structure and membrane protein trafficking","volume":"197","author":"Liem","year":"2012","journal-title":"J Cell Biol."},{"key":"2025030619392966400_awae331-B51","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1016\/j.devcel.2012.04.009","article-title":"IFT25 links the signal-dependent movement of hedgehog components to intraflagellar transport","volume":"22","author":"Keady","year":"2012","journal-title":"Dev Cell."},{"key":"2025030619392966400_awae331-B52","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/S0092-8674(00)80678-9","article-title":"Hedgehog-regulated processing of Gli3 produces an anterior\/posterior repressor gradient in the developing vertebrate limb","volume":"100","author":"Wang","year":"2000","journal-title":"Cell"},{"key":"2025030619392966400_awae331-B53","doi-asserted-by":"crossref","first-page":"11325","DOI":"10.1073\/pnas.0505328102","article-title":"Cilia and hedgehog responsiveness in the mouse","volume":"102","author":"Huangfu","year":"2005","journal-title":"Proc Natl Acad Sci U S A."},{"key":"2025030619392966400_awae331-B54","doi-asserted-by":"crossref","first-page":"e53","DOI":"10.1371\/journal.pgen.0010053","article-title":"Gli2 and Gli3 localize to cilia and require the intraflagellar transport protein polaris for processing and function","volume":"1","author":"Haycraft","year":"2005","journal-title":"PLoS Genet."},{"key":"2025030619392966400_awae331-B55","doi-asserted-by":"crossref","first-page":"1910","DOI":"10.1128\/MCB.01089-09","article-title":"Kinetics of hedgehog-dependent full-length Gli3 accumulation in primary cilia and subsequent degradation","volume":"30","author":"Wen","year":"2010","journal-title":"Mol Cell Biol."},{"key":"2025030619392966400_awae331-B56","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1038\/s41467-017-00911-y","article-title":"HDAC6 inhibition reverses axonal transport defects in motor neurons derived from FUS-ALS patients","volume":"8","author":"Guo","year":"2017","journal-title":"Nat Commun."},{"key":"2025030619392966400_awae331-B57","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.abg3013","article-title":"C9orf72-derived arginine-containing dipeptide repeats associate with axonal transport machinery and impede microtubule-based motility","volume":"7","author":"Fumagalli","year":"2021","journal-title":"Sci Adv."},{"key":"2025030619392966400_awae331-B58","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1186\/1471-2202-14-119","article-title":"Trophic and proliferative effects of Shh on motor neurons in embryonic spinal cord culture from wildtype and G93A SOD1 mice","volume":"14","author":"Ma","year":"2013","journal-title":"BMC Neurosci."},{"key":"2025030619392966400_awae331-B59","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1186\/s40478-024-01852-6","article-title":"ALS-associated C21ORF2 variant disrupts DNA damage repair, mitochondrial metabolism, neuronal excitability and NEK1 levels in human motor neurons","volume":"12","author":"Zelina","year":"2024","journal-title":"Acta Neuropathol Commun"},{"key":"2025030619392966400_awae331-B60","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/s41467-017-02729-0","article-title":"C9ORF72 repeat expansion causes vulnerability of motor neurons to Ca2+-permeable AMPA receptor-mediated excitotoxicity","volume":"9","author":"Selvaraj","year":"2018","journal-title":"Nat Commun."},{"key":"2025030619392966400_awae331-B61","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1023\/A:1006906415388","article-title":"Studies of the type I cellular retinoic acid-binding protein mutants and their biological activities","volume":"200","author":"Wei","year":"1999","journal-title":"Mol Cell Biochem."},{"key":"2025030619392966400_awae331-B62","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s40035-018-0135-7","article-title":"GM604 regulates developmental neurogenesis pathways and the expression of genes associated with amyotrophic lateral sclerosis","volume":"7","author":"Swindell","year":"2018","journal-title":"Transl Neurodegener."},{"key":"2025030619392966400_awae331-B63","doi-asserted-by":"crossref","first-page":"4125","DOI":"10.3390\/ijms21114125","article-title":"Sonic hedgehog-gli1 signaling and cellular retinoic acid binding protein 1 gene regulation in motor neuron differentiation and diseases","volume":"21","author":"Lin","year":"2020","journal-title":"Int J Mol Sci."},{"key":"2025030619392966400_awae331-B64","doi-asserted-by":"crossref","first-page":"1744","DOI":"10.1038\/s41418-022-00959-4","article-title":"CRABP1-CaMKII-Agrn regulates the maintenance of neuromuscular junction in spinal motor neuron","volume":"29","author":"Lin","year":"2022","journal-title":"Cell Death Differ."},{"key":"2025030619392966400_awae331-B65","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s13024-022-00591-3","article-title":"FUS-ALS hiPSC-derived astrocytes impair human motor units through both gain-of-toxicity and loss-of-support mechanisms","volume":"18","author":"Stoklund Dittlau","year":"2023","journal-title":"Mol Neurodegener."},{"key":"2025030619392966400_awae331-B66","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1080\/00207454.2020.1773821","article-title":"Protease nexin-1 protects against Alzheimer\u2019s disease by regulating the sonic hedgehog signaling pathway","volume":"131","author":"Li","year":"2020","journal-title":"Int J Neurosci."},{"key":"2025030619392966400_awae331-B67","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s13630-018-0059-y","article-title":"Amyloid-\u03b2 interrupts canonical Sonic hedgehog signaling by distorting primary cilia structure","volume":"7","author":"Vorobyeva","year":"2018","journal-title":"Cilia"},{"key":"2025030619392966400_awae331-B68","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0306-4522(02)00214-2","article-title":"Behavioural and immunohistochemical changes following supranigral administration of sonic hedgehog in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated common marmosets","volume":"114","author":"Dass","year":"2002","journal-title":"Neuroscience"},{"key":"2025030619392966400_awae331-B69","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1111\/jnc.14064","article-title":"Sonic hedgehog signalling mediates astrocyte crosstalk with neurons to confer neuroprotection","volume":"142","author":"Ugbode","year":"2017","journal-title":"J Neurochem."},{"key":"2025030619392966400_awae331-B70","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1080\/15548627.2024.2311541","article-title":"The C9orf72-SMCR8 complex suppresses primary ciliogenesis as a RAB8A GAP","volume":"20","author":"Tang","year":"2024","journal-title":"Autophagy"},{"key":"2025030619392966400_awae331-B71","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1186\/s40478-023-01648-0","article-title":"A toxic gain-of-function mechanism in C9orf72 ALS impairs the autophagy-lysosome pathway in neurons","volume":"11","author":"Becker","year":"2023","journal-title":"Acta Neuropathol Commun"},{"key":"2025030619392966400_awae331-B72","doi-asserted-by":"crossref","first-page":"6456","DOI":"10.1038\/sj.onc.1210459","article-title":"Frequent methylation-associated silencing of a candidate tumor-suppressor, CRABP1, in esophageal squamous-cell carcinoma","volume":"26","author":"Tanaka","year":"2007","journal-title":"Oncogene"},{"key":"2025030619392966400_awae331-B73","doi-asserted-by":"crossref","first-page":"53","DOI":"10.4137\/GEG.S40847","article-title":"DNA methylation of cellular retinoic acid-binding proteins in cervical cancer","volume":"8","author":"Arellano-Ortiz","year":"2016","journal-title":"Genet Epigenet."},{"key":"2025030619392966400_awae331-B74","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1186\/s12974-017-0958-7","article-title":"Primary cilia modulate TLR4-mediated inflammatory responses in hippocampal neurons","volume":"14","author":"Baek","year":"2017","journal-title":"J Neuroinflammation."},{"key":"2025030619392966400_awae331-B75","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1038\/nature12606","article-title":"Autophagy promotes primary ciliogenesis by removing OFD1 from centriolar satellites","volume":"502","author":"Tang","year":"2013","journal-title":"Nature"},{"key":"2025030619392966400_awae331-B76","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1038\/cdd.2014.171","article-title":"Autophagy and regulation of cilia function and assembly","volume":"22","author":"Orhon","year":"2015","journal-title":"Cell Death Differ."},{"key":"2025030619392966400_awae331-B77","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1038\/nature12639","article-title":"Functional interaction between autophagy and ciliogenesis","volume":"502","author":"Pampliega","year":"2013","journal-title":"Nature"}],"container-title":["Brain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/brain\/advance-article-pdf\/doi\/10.1093\/brain\/awae331\/61235342\/awae331.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/brain\/article-pdf\/148\/3\/803\/61235342\/awae331.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/brain\/article-pdf\/148\/3\/803\/61235342\/awae331.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T14:47:17Z","timestamp":1741272437000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/brain\/article\/148\/3\/803\/7928515"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,20]]},"references-count":77,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,12,20]]},"published-print":{"date-parts":[[2025,3,6]]}},"URL":"https:\/\/doi.org\/10.1093\/brain\/awae331","relation":{},"ISSN":["0006-8950","1460-2156"],"issn-type":[{"value":"0006-8950","type":"print"},{"value":"1460-2156","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,3]]},"published":{"date-parts":[[2024,12,20]]}}}