C9ORF72 hexanucleotide repeat expansion: From ALS and FTD to a broader pathogenic role?

被引:4
作者
Sellier, C. [1 ]
Corcia, P. [2 ,3 ]
Vourc'h, P. [2 ,4 ]
Dupuis, L. [1 ]
机构
[1] Univ Strasbourg, Inserm, UMR S1329, Ctr Rech Biomd Strasbourg, Strasbourg, France
[2] Univ Tours, UMR iBrain 1253, Inserm, Tours, France
[3] CHU Bretonneau, Ctr Constitut Coordinat SLA, 2 Blvd Tonnelle, F-37044 Tours 1, France
[4] CHU Tours, Serv Biochim & Biol Mol, Tours, France
关键词
Amyotrophic lateral sclerosis; C9ORF72; Phenotype; Pathophysiology; AMYOTROPHIC-LATERAL-SCLEROSIS; FRONTOTEMPORAL LOBAR DEGENERATION; RNA FOCI; GGGGCC REPEAT; ANTISENSE TRANSCRIPTS; RAN TRANSLATION; CPG-ISLAND; PROTEINS; DISEASE; GENE;
D O I
10.1016/j.neurol.2024.03.008
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
The major gene underlying monogenic forms of amyotrophic lateral sclerosis (ALS) and fronto-temporal dementia (FTD) is C9ORF72. The causative mutation in C9ORF72 is an abnormal hexanucleotide (G4C2) repeat expansion (HRE) located in the first intron of the gene. The aim of this review is to propose a comprehensive update on recent developments on clinical, biological and therapeutics aspects related to C9ORF72 in order to highlight the current understanding of genotype -phenotype correlations, and also on biological machinery leading to neuronal death. We will particularly focus on the broad phenotypic presentation of C9ORF72-related diseases, that goes well beyond the classical phenotypes observed in ALS and FTD patients. Last, we will comment the possible therapeutical hopes for patients carrying a C9ORF72 HRE. # 2024 The Author(s). Published by Elsevier Masson SAS. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
引用
收藏
页码:417 / 428
页数:12
相关论文
共 159 条
[1]   p62 positive, TDP-43 negative, neuronal cytoplasmic and intranuclear inclusions in the cerebellum and hippocampus define the pathology of C9orf72-linked FTLD and MND/ALS [J].
Al-Sarraj, Safa ;
King, Andrew ;
Troakes, Claire ;
Smith, Bradley ;
Maekawa, Satomi ;
Bodi, Istvan ;
Rogelj, Boris ;
Al-Chalabi, Ammar ;
Hortobagyi, Tibor ;
Shaw, Christopher E. .
ACTA NEUROPATHOLOGICA, 2011, 122 (06) :691-702
[2]   C9orf72 Hexanucleotide Repeat in Huntington-Like Patients: Systematic Review and Meta-Analysis [J].
Alva-Diaz, Carlos ;
Alarcon-Ruiz, Christoper A. ;
Pacheco-Barrios, Kevin ;
Mori, Nicanor ;
Pacheco-Mendoza, Josmel ;
Traynor, Bryan J. ;
Rivera-Valdivia, Andrea ;
Lertwilaiwittaya, Pongtawat ;
Bird, Thomas D. ;
Cornejo-Olivas, Mario .
FRONTIERS IN GENETICS, 2020, 11
[3]   C9orf72 binds SMCR8, localizes to lysosomes, and regulates mTORC1 signaling [J].
Amick, Joseph ;
Roczniak-Ferguson, Agnes ;
Ferguson, Shawn M. .
MOLECULAR BIOLOGY OF THE CELL, 2016, 27 (20) :3040-3051
[4]   Regulation of autophagy by the Rab GTPase network [J].
Ao, X. ;
Zou, L. ;
Wu, Y. .
CELL DEATH AND DIFFERENTIATION, 2014, 21 (03) :348-358
[5]   C9orf72 and RAB7L1 regulate vesicle trafficking in amyotrophic lateral sclerosis and frontotemporal dementia [J].
Aoki, Yoshitsugu ;
Manzano, Raquel ;
Lee, Yi ;
Dafinca, Ruxandra ;
Aoki, Misako ;
Douglas, Andrew G. L. ;
Varela, Miguel A. ;
Sathyaprakash, Chaitra ;
Scaber, Jakub ;
Barbagallo, Paola ;
Vader, Pieter ;
Mager, Imre ;
Ezzat, Kariem ;
Turner, Martin R. ;
Ito, Naoki ;
Gasco, Samanta ;
Ohbayashi, Norihiko ;
El Andaloussi, Samir ;
Takeda, Shin'ichi ;
Fukuda, Mitsunori ;
Talbot, Kevin ;
Wood, Matthew J. A. .
BRAIN, 2017, 140 :887-897
[6]   Unconventional Translation of C9ORF72 GGGGCC Expansion Generates Insoluble Polypeptides Specific to c9FTD/ALS [J].
Ash, Peter E. A. ;
Bieniek, Kevin F. ;
Gendron, Tania F. ;
Caulfield, Thomas ;
Lin, Wen-Lang ;
DeJesus-Hernandez, Mariely ;
van Blitterswijk, Marka M. ;
Jansen-West, Karen ;
Paul, Joseph W., III ;
Rademakers, Rosa ;
Boylan, Kevin B. ;
Dickson, Dennis W. ;
Petrucelli, Leonard .
NEURON, 2013, 77 (04) :639-646
[7]   C9orf72 ablation causes immune dysregulation characterized by leukocyte expansion, autoantibody production, and glomerulonephropathy in mice [J].
Atanasio, Amanda ;
Decman, Vilma ;
White, Derek ;
Ramos, Meg ;
Ikiz, Burcin ;
Lee, Hoi-Ching ;
Siao, Chia-Jen ;
Brydges, Susannah ;
LaRosa, Elizabeth ;
Bai, Yu ;
Fury, Wen ;
Burfeind, Patricia ;
Zamfirova, Ralica ;
Warshaw, Gregg ;
Orengo, Jamie ;
Oyejide, Adelekan ;
Fralish, Michael ;
Auerbach, Wojtek ;
Poueymirou, William ;
Freudenberg, Jan ;
Gong, Guochun ;
Zambrowicz, Brian ;
Valenzuela, David ;
Yancopoulos, George ;
Murphy, Andrew ;
Thurston, Gavin ;
Lai, Ka-Man Venus .
SCIENTIFIC REPORTS, 2016, 6
[8]   C9ORF72 expression and cellular localization over mouse development [J].
Atkinson, Rachel A. K. ;
Fernandez-Martos, Carmen M. ;
Atkin, Julie D. ;
Vickers, James C. ;
King, Anna E. .
ACTA NEUROPATHOLOGICA COMMUNICATIONS, 2015, 3 :59
[9]   An interaction between synapsin and C9orf72 regulates excitatory synapses and is impaired in ALS/FTD [J].
Bauer, Claudia S. ;
Cohen, Rebecca N. ;
Sironi, Francesca ;
Livesey, Matthew R. ;
Gillingwater, Thomas H. ;
Highley, J. Robin ;
Fillingham, Daniel J. ;
Coldicott, Ian ;
Smith, Emma F. ;
Gibson, Yolanda B. ;
Webster, Christopher P. ;
Grierson, Andrew J. ;
Bendotti, Caterina ;
De Vos, Kurt J. .
ACTA NEUROPATHOLOGICA, 2022, 144 (03) :437-464
[10]   Large C9orf72 Hexanucleotide Repeat Expansions Are Seen in Multiple Neurodegenerative Syndromes and Are More Frequent Than Expected in the UK Population [J].
Beck, Jon ;
Poulter, Mark ;
Hensman, Davina ;
Rohrer, Jonathan D. ;
Mahoney, Colin J. ;
Adamson, Gary ;
Campbell, Tracy ;
Uphill, James ;
Borg, Aaron ;
Fratta, Pietro ;
Orrell, Richard W. ;
Malaspina, Andrea ;
Rowe, James ;
Brown, Jeremy ;
Hodges, John ;
Sidle, Katie ;
Polke, James M. ;
Houlden, Henry ;
Schott, Jonathan M. ;
Fox, Nick C. ;
Rossor, Martin N. ;
Tabrizi, Sarah J. ;
Isaacs, Adrian M. ;
Hardy, John ;
Warren, Jason D. ;
Collinge, John ;
Mead, Simon .
AMERICAN JOURNAL OF HUMAN GENETICS, 2013, 92 (03) :345-353