Mutations in CHMP2B in Lower Motor Neuron Predominant Amyotrophic Lateral Sclerosis (ALS)
Open accessAbstract
BACKGROUND: Amyotrophic lateral sclerosis (ALS), a common late-onset neurodegenerative disease, is associated with fronto-temporal dementia (FTD) in 3-10% of patients. A mutation in CHMP2B was recently identified in a Danish pedigree with autosomal dominant FTD. Subsequently, two unrelated patients with familial ALS, one of whom also showed features of FTD, were shown to carry missense mutations in CHMP2B. The initial aim of this study was to determine whether mutations in CHMP2B contribute more broadly to ALS pathogenesis. METHODOLOGY/PRINCIPAL FINDINGS: Sequencing of CHMP2B in 433 ALS cases from the North of England identified 4 cases carrying 3 missense mutations, including one novel mutation, p.Thr104Asn, none of which were present in 500 neurologically normal controls. Analysis of clinical and neuropathological data of these 4 cases showed a phenotype consistent with the lower motor neuron predominant (progressive muscular atrophy (PMA)) variant of ALS. Only one had a recognised family history of ALS and none had clinically apparent dementia. Microarray analysis of motor neurons from CHMP2B cases, compared to controls, showed a distinct gene expression signature with significant differential expression predicting disassembly of cell structure; increased calcium concentration in the ER lumen; decrease in the availability of ATP; down-regulation of the classical and p38 MAPK signalling pathways, reduction in autophagy initiation and a global repression of translation. Transfection of mutant CHMP2B into HEK-293 and COS-7 cells resulted in the formation of large cytoplasmic vacuoles, aberrant lysosomal localisation demonstrated by CD63 staining and impairment of autophagy indicated by increased levels of LC3-II protein. These changes were absent in control cells transfected with wild-type CHMP2B. CONCLUSIONS/SIGNIFICANCE: We conclude that in a population drawn from North of England pathogenic CHMP2B mutations are found in approximately 1% of cases of ALS and 10% of those with lower motor neuron predominant ALS. We provide a body of evidence indicating the likely pathogenicity of the reported gene alterations. However, absolute confirmation of pathogenicity requires further evidence, including documentation of familial transmission in ALS pedigrees which might be most fruitfully explored in cases with a LMN predominant phenotype.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Motor neurons from CHMP2B mutant ALS patients show increased calcium concentrations, reduced ATP availability, downregulation of the MAPK/p38 signaling pathway, and impaired autophagy initiation.
“Motor neurons from CHMP2B mutant ALS patients show increased calcium concentrations, reduced ATP availability, downregulation of the MAPK/p38 signaling pathway and impaired autophagy initiation [266].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [266]
Overexpression of CHMP2B mutants leads to the formation of large cytoplasmic vacuoles and increased LC3-II protein levels.
“overexpression of CHMP2B mutants leads to the formation of large cytoplasmic vacuoles and increased LC3-II protein levels [266]”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [266]
CHMP2B mutations were subsequently identified in ALS patients with a lower motor neuron predominant syndrome.
“CHMP2B mutations were subsequently identified in ALS patients with a lower motor neuron predominant syndrome [266,267].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [266]
Disease-associated CHMP2B mutations disrupt autophagy.
“suggesting that disease-associated CHMP2B mutations disrupt autophagy.”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [266]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860 · see citing works
Calcium's Role in Mechanotransduction during Muscle Development
Damm, T. B., & Egli, M. (2014) · Cellular Physiology and Biochemistry · doi:10.1159/000356667 · Cited by 14,548 · see citing works
DAVID: Database for Annotation, Visualization, and Integrated Discovery
Dennis, G., Sherman, B. T., Hosack, D. A., Yang, J., Gao, W., Lane, H. C., & Lempicki, R. A. (2003) · Genome Biology · doi:10.1186/gb-2003-4-5-p3 · Cited by 9,327 · see citing works
Rosen, D. R., Siddique, T., Patterson, D., Figlewicz, D. A., Sapp, P., Hentati, A., Donaldson, D., Goto, J., O'Regan, J. P., Deng, H.-X., et al. (1993) · Nature · doi:10.1038/362059a0 · Cited by 7,062 · see citing works
Upstream and downstream of mTOR
Hay, N., & Sonenberg, N. (2004) · Genes & Development · doi:10.1101/gad.1212704 · Cited by 4,181 · see citing works
Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice
Hara, T., Nakamura, K., Matsui, M., Yamamoto, A., Nakahara, Y., Suzuki-Migishima, R., Yokoyama, M., Mishima, K., Saito, I., Okano, H., et al. (2006) · Nature · doi:10.1038/nature04724 · Cited by 3,882 · see citing works
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837 · see citing works
Loss of autophagy in the central nervous system causes neurodegeneration in mice
Komatsu, M., Waguri, S., Chiba, T., Murata, S., Iwata, J.-I., Tanida, I., Ueno, T., Koike, M., Uchiyama, Y., Kominami, E., et al. (2006) · Nature · doi:10.1038/nature04723 · Cited by 3,500 · see citing works
Arai, T., Hasegawa, M., Akiyama, H., Ikeda, K., Nonaka, T., Mori, H., Mann, D., Tsuchiya, K., Yoshida, M., Hashizume, Y., et al. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.10.093 · Cited by 2,732 · see citing works
Roux, P. P., & Blenis, J. (2004) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.68.2.320-344.2004 · Cited by 2,494 · see citing works
DAVID: Database for Annotation, Visualization, and Integrated Discovery
Dennis, G., Sherman, B. T., Hosack, D. A., Yang, J., Gao, W., Lane, H. C., & Lempicki, R. A. (2003) · Genome biology · doi:10.1186/gb-2003-4-9-r60 · Cited by 2,383 · see citing works
Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes
Klionsky, D. J., Abeliovich, H., Agostinis, P., Agrawal, D. K., Aliev, G., Askew, D. S., Baba, M., Baehrecke, E. H., Bahr, B. A., Ballabio, A., et al. (2008) · Autophagy · doi:10.4161/auto.5338 · Cited by 2,230 · see citing works
Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17
Baker, M., Mackenzie, I. R., Pickering-Brown, S. M., Gass, J., Rademakers, R., Lindholm, C., Snowden, J., Adamson, J., Sadovnick, A. D., Rollinson, S., et al. (2006) · Nature · doi:10.1038/nature05016 · Cited by 2,058 · see citing works
Katzmann, D. J., Babst, M., & Emr, S. D. (2001) · Cell · doi:10.1016/s0092-8674(01)00434-2 · Cited by 1,430 · see citing works
Holz, M. K., Ballif, B. A., Gygi, S. P., & Blenis, J. (2005) · Cell · doi:10.1016/j.cell.2005.10.024 · Cited by 1,262 · see citing works
Amplified RNA synthesized from limited quantities of heterogeneous cDNA.
Gelder, R. N. V., von Zastrow, M., Yool, A., Dement, W. C., Barchas, J. D., & Eberwine, J. H. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.5.1663 · Cited by 1,262 · see citing works
Phosphatidic Acid-Mediated Mitogenic Activation of mTOR Signaling
Fang, Y., Vilella-Bach, M., Bachmann, R., Flanigan, A., & Chen, J. (2001) · Science · doi:10.1126/science.1066015 · Cited by 1,055 · see citing works
Nishimura, A. L., Mitne‐Neto, M., da Silva, H. C. A., Richieri‐Costa, A., Middleton, S., Cascio, D., Kok, F., de Oliveira, J. R. M., Gillingwater, T. H., Webb, J., et al. (2004) · The American Journal of Human Genetics · doi:10.1086/425287 · Cited by 995 · see citing works
Mackenzie, I. R. A., Bigio, E. H., Ince, P. G., Geser, F., Neumann, M., Cairns, N. J., Kwong, L. K., Forman, M. S., Ravits, J., Stewart, H., et al. (2007) · Annals of Neurology · doi:10.1002/ana.21147 · Cited by 992 · see citing works
Self-citationThe MAP1 family of microtubule-associated proteins.
Dehmelt (2004) · Genome biology · doi:10.1186/gb-2004-6-1-204 · Cited by 972 · see citing works
Kim, D., Sarbassov, D. D., Ali, S. M., Latek, R. R., Guntur, K., Erdjument‐Bromage, H., Tempst, P., & Sabatini, D. M. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00114-x · Cited by 955 · see citing works
Rosen, D. (1993) · Nature · doi:10.1038/364362c0 · Cited by 922 · see citing works
Babst, M., Katzmann, D. J., Estepa, E. J., Meerloo, T., & Emr, S. D. (2002) · Developmental Cell · doi:10.1016/s1534-5807(02)00220-4 · Cited by 875 · see citing works
Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal dementia
Skibinski, G., Parkinson, N. J., Brown, J. M., Chakrabarti, L., Lloyd, S. L., Hummerich, H., Nielsen, J. E., Hodges, J. R., Spillantini, M. G., Thusgaard, T., et al. (2005) · Nature Genetics · doi:10.1038/ng1609 · Cited by 822 · see citing works
Babst, M., Wendland, B., Estepa, E. J., & Emr, S. D. (1998) · The EMBO Journal · doi:10.1093/emboj/17.11.2982 · Cited by 770 · see citing works
Trafficking and function of the tetraspanin CD63
Pols, M. S., & Klumperman, J. (2009) · Experimental Cell Research · doi:10.1016/j.yexcr.2008.09.020 · Cited by 745 · see citing works
Role of Axonal Transport in Neurodegenerative Diseases
Vos, K. J. D., Grierson, A. J., Ackerley, S., & Miller, C. C. J. (2008) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.31.061307.090711 · Cited by 734 · see citing works
Self-citationFilimonenko, M., Stuffers, S., Raiborg, C., Yamamoto, A., Malerød, L., Fisher, E. M. C., Isaacs, A., Brech, A., Stenmark, H., & Simonsen, A. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200702115 · Cited by 626 · see citing works
In search of an “autophagomometer”
Rubinsztein, D. C., Cuervo, A. M., Ravikumar, B., Sarkar, S., Korolchuk, V. I., Kaushik, S., & Klionsky, D. J. (2009) · Autophagy · doi:10.4161/auto.5.5.8823 · Cited by 551 · see citing works
The mTOR/PI3K and MAPK pathways converge on eIF4B to control its phosphorylation and activity
Shahbazian, D., Roux, P. P., Mieulet, V., Cohen, M. S., Raught, B., Taunton, J., Hershey, J. W. B., Blenis, J., Pende, M., & Sonenberg, N. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601166 · Cited by 532 · see citing works
Ueda, T., Watanabe-Fukunaga, R., Fukuyama, H., Nagata, S., & Fukunaga, R. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.15.6539-6549.2004 · Cited by 507 · see citing works
ESCRT-III Dysfunction Causes Autophagosome Accumulation and Neurodegeneration
Lee, J., Beigneux, A. P., Ahmad, S. T., Young, S. G., & Gao, F. (2007) · Current Biology · doi:10.1016/j.cub.2007.07.029 · Cited by 490 · see citing works
Phosphorylation of eucaryotic translation initiation factor 4B Ser422 is modulated by S6 kinases
Raught, B., Peiretti, F., Gingras, A., Livingstone, M., Shahbazian, D., Mayeur, G. L., Polakiewicz, R. D., Sonenberg, N., & Hershey, J. W. B. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600193 · Cited by 473 · see citing works
Autophagy and neurodegeneration: when the cleaning crew goes on strike
Martínez‐Vicente, M., & Cuervo, A. M. (2007) · The Lancet Neurology · doi:10.1016/s1474-4422(07)70076-5 · Cited by 472 · see citing works
Atomic structure and chemistry of human serum albumin
He, X. M., & Carter, D. C. (1993) · Nature · doi:10.1038/364362b0 · Cited by 415 · see citing works
Mitochondria: The Hub of Cellular Ca2+Signaling
Szabadkai, G., & Duchen, M. R. (2008) · Physiology · doi:10.1152/physiol.00046.2007 · Cited by 403 · see citing works
ALS phenotypes with mutations in <i>CHMP2B</i> (charged multivesicular body protein 2B)
Parkinson, N., Ince, P. G., Smith, M. O., Highley, R., Skibinski, G., Andersen, P. M., Morrison, K. E., Pall, H. S., Hardiman, O., Collinge, J., et al. (2006) · Neurology · doi:10.1212/01.wnl.0000231510.89311.8b · Cited by 395 · see citing works
Self-citationHeat Shock Protein 27 Controls Apoptosis by Regulating Akt Activation
Rane, M. J., Pan, Y., Singh, S. P., Powell, D. W., Wu, R., Cummins, T. D., Chen, Q., McLeish, K. R., & Klein, J. B. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m303417200 · Cited by 367 · see citing works
A rational mechanism for combination treatment of Huntington's disease using lithium and rapamycin
Sarkar, S., Krishna, G., Imarisio, S., Saiki, S., O’Kane, C. J., & Rubinsztein, D. C. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddm294 · Cited by 348 · see citing works
Andersen, P. M., Nilsson, P., Ala‐Hurula, V., Keränen, M.-L., Tarvainen, I., Haltia, T., Nilsson, L., Binzer, M., Forsgren, L., & Marklund, S. L. (1995) · Nature Genetics · doi:10.1038/ng0595-61 · Cited by 323 · see citing works
Molecular and cellular pathways of neurodegeneration in motor neurone disease
Shaw, P. J. (2005) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2004.048652 · Cited by 311 · see citing works
Self-citationCorticospinal tract degeneration in the progressive muscular atrophy variant of ALS
Ince, P. G., Evans, J., Knopp, M. V., Forster, G., Hamdalla, H. H. M., Wharton, S. B., & Shaw, P. J. (2003) · Neurology · doi:10.1212/01.wnl.0000058901.75728.4e · Cited by 303 · see citing works
Self-citationCheong, H., Nair, U., Geng, J., & Klionsky, D. J. (2007) · Molecular Biology of the Cell · doi:10.1091/mbc.e07-08-0826 · Cited by 262 · see citing works
The MAP1 family of microtubule-associated proteins
Halpain, S., & Dehmelt, L. (2006) · Genome Biology · doi:10.1186/gb-2006-7-6-224 · Cited by 261 · see citing works
Endoplasmic reticulum stress response and neurodegeneration
Paschen, W., & Mengesdorf, T. (2005) · Cell Calcium · doi:10.1016/j.ceca.2005.06.019 · Cited by 252 · see citing works
Fragmentation of the Golgi apparatus in neurodegenerative diseases and cell death
Gonatas, N. K., Stieber, A., & Gonatas, J. O. (2006) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2006.01.019 · Cited by 236 · see citing works
Ferraiuolo, L., Heath, P. R., Holden, H. M., Kasher, P. R., Kirby, J., & Shaw, P. J. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.1470-07.2007 · Cited by 198 · see citing works
Self-citationCorcelle–Termeau, E., Djerbi, N., Mari, M., Nebout, M., Fiorini, C., Fénichel, P., Hofman, P. M., Poujeol, P., & Mograbi, B. (2007) · Autophagy · doi:10.4161/auto.3424 · Cited by 184 · see citing works
Molecular Neuropathology of TDP-43 Proteinopathies
Neumann, M. (2009) · International Journal of Molecular Sciences · doi:10.3390/ijms10010232 · Cited by 169 · see citing works
van der Zee, J., Urwin, H., Engelborghs, S., Bruyland, M., Vandenberghe, R., Dermaut, B., De Pooter, T., Peeters, K., Santens, P., De Deyn, P. P., et al. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddm309 · Cited by 167 · see citing works
Hadano, S., Benn, S. C., Kakuta, S., Otomo, A., Sudo, K., Kunita, R., Suzuki-Utsunomiya, K., Mizumura, H., Shefner, J. M., Cox, G. A., et al. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi440 · Cited by 138 · see citing works
Jackson, M. T., Al‐Chalabi, A., Enayat, Z. E., Chioza, B. A., Leigh, P., & Morrison, K. E. (1997) · Annals of Neurology · doi:10.1002/ana.410420518 · Cited by 130 · see citing works
Self-citationLee, J., & Gao, F. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.0924-09.2009 · Cited by 124 · see citing works
Strey, C. W., Spellman, D. S., Stieber, A., Gonatas, J. O., Wang, X., Lambris, J. D., & Gonatas, N. K. (2004) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63426-8 · Cited by 102 · see citing works
Lekmine, F., Sassano, A., Uddin, S., Smith, J. G., Majchrzak, B., Brachmann, S., Hay, N., Fish, E., & Platanias, L. (2004) · Experimental Cell Research · doi:10.1016/j.yexcr.2003.12.021 · Cited by 99 · see citing works
The Rab5 Activator ALS2/alsin Acts as a Novel Rac1 Effector through Rac1-activated Endocytosis
Kunita, R., Otomo, A., Mizumura, H., Suzuki-Utsunomiya, K., Hadano, S., & Ikeda, J. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m610682200 · Cited by 88 · see citing works
Use1p is a yeast SNARE protein required for retrograde traffic to the ER
Dilcher, M., Veith, B., Chidambaram, S., et al. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg339 · Cited by 88 · see citing works
Neuronal inclusion protein TDP-43 has no primary genetic role in FTD and ALS
Gijselinck, I., Sleegers, K., Engelborghs, S., Robberecht, W., Martin, J., Vandenberghe, R. R., Sciot, R., Dermaut, B., Goossens, D., van der Zee, J., et al. (2008) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.11.002 · Cited by 85 · see citing works
Hadano, S., Kunita, R., Otomo, A., Suzuki-Utsunomiya, K., & Ikeda, J. (2007) · Neurochemistry International · doi:10.1016/j.neuint.2007.04.010 · Cited by 83 · see citing works
British motor neuron disease twin study.
Graham, A., Macdonald, A., & Hawkes, C. H. (1997) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.62.6.562 · Cited by 76 · see citing works
van Es, M. A., Dahlberg, C., Birve, A., Veldink, J. H., van den Berg, L. H., & Andersen, P. M. (2009) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2009.181453 · Cited by 76 · see citing works
TDP-43 Is Not a Common Cause of Sporadic Amyotrophic Lateral Sclerosis
Guerreiro, R. J., Schymick, J. C., Crews, C. K., Singleton, A., Hardy, J., & Traynor, B. J. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002450 · Cited by 70 · see citing works
CHMP2B mutations are not a common cause of frontotemporal lobar degeneration
Cannon, A. D., Baker, M., Boeve, B. F., Josephs, K. A., Knopman, D. S., Petersen, R. C., Parisi, J. E., Dickison, D., Adamson, J. L., Snowden, J. S., et al. (2006) · Neuroscience Letters · doi:10.1016/j.neulet.2005.12.056 · Cited by 62 · see citing works
Motor neuron disease in a patient with a mitochondrial tRNAIle mutation
Borthwick, G. M., Taylor, R. W., Walls, T. J., Tońska, K., Taylor, G. A., Shaw, P. J., Ince, P. G., & Turnbull, D. M. (2005) · Annals of Neurology · doi:10.1002/ana.20758 · Cited by 51 · see citing works
Self-citationIdentification of a novel exon 4 SOD1 mutation in a sporadic amyotrophic lateral sclerosis patient
Jones, C. T., Shaw, P. J., Chari, G., et al. (1994) · Molecular and Cellular Probes · doi:10.1006/mcpr.1994.1046 · Cited by 49 · see citing works
Self-citationAutophagy defects contribute to neurodegeneration induced by dysfunctional ESCRT-III
Lee, J., Liu, L., & Gao, F. (2009) · Autophagy · doi:10.4161/auto.5.7.9823 · Cited by 38 · see citing works
Miyamoto, S., Patel, P., & Hershey, J. W. B. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m414129200 · Cited by 35 · see citing works
Genetics of Amyotrophic Lateral Sclerosis
Siddique, N., & Siddique, T. (2008) · Physical Medicine and Rehabilitation Clinics of North America · doi:10.1016/j.pmr.2008.05.001 · Cited by 33 · see citing works
ALS phenotypes with mutations in CHMP2B (charged multivesicular body protein 2B)
Parkinson, N. (2006) · Neurology · doi:10.1212/01.wnl.0000236199.11821.85 · Cited by 33 · see citing works
ESCRT-III Dysfunction Causes Autophagosome Accumulation and Neurodegeneration
Lee, J.-A., Beigneux, A. P., Ahmad, S. T., Young, S. G., & Gao, F. (2007) · Current Biology · doi:10.1016/j.cub.2007.08.057 · Cited by 25 · see citing works
A thorough assessment of benign genetic variability inGRNandMAPT
Guerreiro, R. J., Washecka, N., Hardy, J., & Singleton, A. (2009) · Human Mutation · doi:10.1002/humu.21152 · Cited by 20 · see citing works
Molecular and Cellular Pathways of Neurodegeneration in Motor Neurone Disease
Shaw, P. J. (2006) · IMPERIAL COLLEGE PRESS eBooks · doi:10.1142/9781860948961_0006 · Cited by 19 · see citing works
Self-citationBrockington, A., Wokke, B. H. A., Hollinger, H. C., et al. (2007) · BMC Medical Genetics · doi:10.1186/1471-2350-8-23 · Cited by 16 · see citing works
Self-citationCHMP2B mutations are not a common cause of familial or sporadic amyotrophic lateral sclerosis
Blair, I. P., Vance, C. A., Durnall, J. C., Williams, K. L., Thoeng, A., Shaw, C. E., & Nicholson, G. A. (2008) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2007.140541 · Cited by 10 · see citing works
Cummins, M. M., Barden, J. A., Cook, D., et al. (2002) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-002-0856-3 · Cited by 9 · see citing works
Shaw, P. J., Ince, P. G., Slade, J. Y., Burn, J., & Cartlidge, N. E. F. (1991) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.54.11.993 · Cited by 8 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Converging Mechanisms in ALS and FTD: Disrupted RNA and Protein Homeostasis
Ling, S.-C., Polymenidou, M., & Cleveland, D. W. (2013) · Neuron · doi:10.1016/j.neuron.2013.07.033 · Cited by 1,811 · see citing works
Molecular pathways of motor neuron injury in amyotrophic lateral sclerosis
Ferraiuolo, L., Kirby, J., Grierson, A. J., Sendtner, M., & Shaw, P. J. (2011) · Nature Reviews Neurology · doi:10.1038/nrneurol.2011.152 · Cited by 615 · see citing works
Self-citationAlmeida, S., Gascon, E., Tran, H., Chou, H. J., Gendron, T. F., DeGroot, S., Tapper, A. R., Sellier, C., Charlet-Berguerand, N., Karydas, A., et al. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1149-y · Cited by 321 · see citing works
The genetics and neuropathology of frontotemporal lobar degeneration
Sieben, A., Van Langenhove, T., Engelborghs, S., Martin, J.-J., Boon, P., Cras, P., De Deyn, P.-P., Santens, P., Van Broeckhoven, C., & Cruts, M. (2012) · Acta Neuropathologica · doi:10.1007/s00401-012-1029-x · Cited by 280 · see citing works
Autophagy and ALS: mechanistic insights and therapeutic implications
Chua, J. P., De Calbiac, H., Kabashi, E., & Barmada, S. J. (2022) · Autophagy · doi:10.1080/15548627.2021.1926656 · Cited by 189 · see citing works
“reduced ATP availability, downregulation of the MAPK/p38 signaling pathway and impaired autophagy initiation [266].”
BackgroundMadill, M., McDonagh, K., Ma, J., Vajda, A., McLoughlin, P., O’Brien, T., Hardiman, O., & Shen, S. (2017) · Molecular Brain · doi:10.1186/s13041-017-0300-4 · Cited by 134 · see citing works
Potential Contribution of Exosomes to the Prion-Like Propagation of Lesions in Alzheimer’s Disease
Vingtdeux, V., Sergeant, N., & Buée, L. (2012) · Frontiers in Physiology · doi:10.3389/fphys.2012.00229 · Cited by 116 · see citing works
Pun, F. W., Liu, B. H. M., Long, X., Leung, H. W., Leung, G. H. D., Mewborne, Q. T., Gao, J., Shneyderman, A., Ozerov, I. V., Wang, J., et al. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.914017 · Cited by 115 · see citing works
“…9 2018 Tam et al., 2019 sALS GSE124439 GPL16791 RNA-seq Motor Cortex – 80 8 2018 Tam et al., 2019 sALS GSE19332 GPL570 Microarray Motor Neurons – 3 7 2009 Cox et al., 2010 sALS GSE76220 GPL9115 RNA-seq Spinal Motor Neurons – 13 8 2015 Krach et al., 2018 sALS GSE67196 GPL11154 RNA-seq Cerebellum…”
Pathogenic role of BECN1/Beclin 1 in the development of amyotrophic lateral sclerosis
Nassif, M., Valenzuela, V., Rojas-Rivera, D., Vidal, R., Matus, S., Castillo, K., Fuentealba, Y., Kroemer, G., Levine, B., & Hetz, C. (2014) · Autophagy · doi:10.4161/auto.28784 · Cited by 100 · see citing works
Liewluck, T., & Saperstein, D. S. (2015) · Neurologic Clinics · doi:10.1016/j.ncl.2015.07.005 · Cited by 65 · see citing works
Inferred divergent gene regulation in archaic hominins reveals potential phenotypic differences
Colbran, L. L., Gamazon, E. R., Zhou, D., Evans, P., Cox, N. J., & Capra, J. A. (2019) · Nature Ecology & Evolution · doi:10.1038/s41559-019-0996-x · Cited by 50 · see citing works
Ho, R., Workman, M. J., Mathkar, P., Wu, K., Kim, K. J., O’Rourke, J. G., Kellogg, M., Montel, V., Banuelos, M. G., Arogundade, O. A., et al. (2021) · Cell Systems · doi:10.1016/j.cels.2020.10.010 · Cited by 62 · see citing works
- Authors
- Cox, L. E., Ferraiuolo, L., Goodall, E. F., Heath, P. R., Higginbottom, A., Mortiboys, H., Hollinger, H. C., Hartley, J. A., Brockington, A., Burness, C. E., Morrison, K. E., Wharton, S. B., Grierson, A. J., Ince, P. G., Kirby, J., & Shaw, P. J.
- Affiliations
- University of Sheffield (GB)
- University of Birmingham (GB)
- Corresponding author
- Shaw, Pamela J.
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2010-03-24
- Volume
- 5
- Issue
- 3
- Pages
- e9872
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC2844426
- OpenAlex
- W2159400623
- Cited by
- 262
- References
- 76
- Citations by year
- 2026: 5 · 2025: 12 · 2024: 9 · 2023: 7 · 2022: 16 · 2021: 11 · 2020: 17 · 2019: 14 · 2018: 13 · 2017: 21 · 2016: 22 · 2015: 23 · 2014: 14 · 2013: 24 · 2012: 33
- FWCI
- 14.70
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
- ePrints Soton (University of Southampton) (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion, other-oa)
- Research Portal (Queen's University Belfast) (submittedVersion)
- Funders
- Wellcome Trust (069388)
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- CHMP2B, amyotrophic lateral sclerosis, progressive muscular atrophy, missense mutations, autophagy dysfunction, MAPK signaling, protein synthesis inhibition, frontotemporal dementia
- MeSH terms
- Aged, Amyotrophic Lateral Sclerosis, Animals, Brain, Chlorocebus aethiops, DNA Mutational Analysis, England, Female, Humans, Male, Middle Aged, Motor Neurons, Mutation, Nerve Tissue Proteins, Spinal Cord, COS Cells, Neurodegenerative Diseases, Mutation, Missense, Oligonucleotide Array Sequence Analysis, Endosomal Sorting Complexes Required for Transport
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
