Gene expression profile of spinal motor neurons in sporadic amyotrophic lateral sclerosis
Abstract
The causative pathomechanism of sporadic amyotrophic lateral sclerosis (ALS) is not clearly understood. Using microarray technology combined with laser-captured microdissection, gene expression profiles of degenerating spinal motor neurons isolated from autopsied patients with sporadic ALS were examined. Gene expression was quantitatively assessed by real-time reverse transcription polymerase chain reaction and in situ hybridization. Spinal motor neurons showed a distinct gene expression profile from the whole spinal ventral horn. Three percent of genes examined were downregulated, and 1% were upregulated in motor neurons. Downregulated genes included those associated with cytoskeleton/axonal transport, transcription, and cell surface antigens/receptors, such as dynactin, microtubule-associated proteins, and early growth response 3 (EGR3). In contrast, cell death-associated genes were mostly upregulated. Promoters for cell death pathway, death receptor 5, cyclins A1 and C, and caspases-1, -3, and -9, were upregulated, whereas cell death inhibitors, acetyl-CoA transporter, and NF-kappaB were also upregulated. Moreover, neuroprotective neurotrophic factors such as ciliary neurotrophic factor (CNTF), Hepatocyte growth factor (HGF), and glial cell line-derived neurotrophic factor were upregulated. Inflammation-related genes, such as those belonging to the cytokine family, were not, however, significantly upregulated in either motor neurons or ventral horns. The motor neuron-specific gene expression profile in sporadic ALS can provide direct information on the genes leading to neurodegeneration and neuronal death and are helpful for developing new therapeutic strategies.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
c-Abl is one of the factors involved in neurodegenerative diseases.
“Accumulating evidence indicate that c-Abl is one of the factors involved in neurodegenerative diseases”
From Nilotinib restores memory function by preventing dopaminergic neuron degeneration in a mouse model of Alzheimer’s Disease (2021) · cites this paper as Jiang et al., 2005
Cites
The sequence of the human genome
Venter, J. C., Adams, M. D., Myers, E. W., Li, P. W., Mural, R. J., Sutton, G. G., Smith, H. O., Yandell, M., Evans, C. A., Holt, R. A., et al. (2001) · Science · doi:10.1126/science.1058040 · Cited by 13,909 · see citing works
Self-citationFrom charcot to lou gehrig: deciphering selective motor neuron death in als
Cleveland, D. W., & Rothstein, J. D. (2001) · Nature reviews. Neuroscience · doi:10.1038/35097565 · Cited by 1,389 · see citing works
Oosthuyse, B., Moons, L., Storkebaum, E., Beck, H., Nuyens, D., Brusselmans, K., Dorpe, J. V., Hellings, P., Gorselink, M., Heymans, S., et al. (2001) · Nature Genetics · doi:10.1038/88842 · Cited by 1,007 · see citing works
Mutant dynactin in motor neuron disease
Puls, I., Jonnakuty, C., LaMonte, B. H., Holzbaur, E. L. F., Tokito, M. K., MANN, E. A., Floeter, M. K., Bidus, K., Drayna, D. T., Oh, S. J., et al. (2003) · Nature Genetics · doi:10.1038/ng1123 · Cited by 961 · see citing works
Lambrechts, D., Storkebaum, E., Morimoto, M., Del‐Favero, J., Smet, F. D., Marklund, S. L., Wyns, S., Thijs, V., Andersson, J., van Marion, I., et al. (2003) · Nature Genetics · doi:10.1038/ng1211 · Cited by 853 · see citing works
Gene expression profiles of laser-captured adjacent neuronal subtypes
Luo, L., Salunga, R. C., Guo, H., Bittner, A., Joy, K. C., Galindo, J. E., Xiao, H., Rogers, K. E., Wan, J. S., Jackson, M. R., et al. (1999) · Nature Medicine · doi:10.1038/4806 · Cited by 691 · see citing works
Williamson, T. L., & Cleveland, D. W. (1999) · Nature Neuroscience · doi:10.1038/4553 · Cited by 638 · see citing works
Classification of pediatric acute lymphoblastic leukemia by gene expression profiling
Ross, M. E., Zhou, X., Song, G., Shurtleff, S. A., Girtman, K., Williams, W. K., Liu, H., Mahfouz, R. A., Raimondi, S. C., Lenny, N. T., et al. (2003) · Blood · doi:10.1182/blood-2003-01-0338 · Cited by 589 · see citing works
RNA editing and death of motor neurons
Kawahara, Y., Ito, K., Sun, H. J., Aizawa, H., Kanazawa, I., & Kwak, S. (2004) · Nature · doi:10.1038/427801a · Cited by 536 · see citing works
Identification of expressed genes by laser-mediated manipulation of single cells
Schüitze, K., & Lahr, G. (1998) · Nature Biotechnology · doi:10.1038/nbt0898-737 · Cited by 431 · see citing works
Zhang, B., Tu, P., Abtahian, F., Trojanowski, J. Q., & Lee, V. M. ‐. (1997) · The Journal of Cell Biology · doi:10.1083/jcb.139.5.1307 · Cited by 299 · see citing works
Kamme, F., Salunga, R. C., Yu, J., Tran, D., Zhu, J. Y., Luo, L., Bittner, A., Guo, H., Miller, N., Wan, J. S., et al. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-09-03607.2003 · Cited by 292 · see citing works
Towards a novel classification of human malignancies based on gene expression patterns
Alizadeh, A. A., Ross, D. T., Perou, C. M., & van de Rijn, M. (2001) · The Journal of Pathology · doi:10.1002/path.889 · Cited by 280 · see citing works
Yoshihara, T., Ishigaki, S., Yamamoto, M., Liang, Y., Jun, Niwa, I., Takeuchi, H., Doyu, M., & Sobue, G. (2001) · Journal of Neurochemistry · doi:10.1046/j.0022-3042.2001.00683.x · Cited by 275 · see citing works
Self-citationSakakibara, S., & Okano, H. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-21-08300.1997 · Cited by 251 · see citing works
Familial amyotrophic lateral sclerosis
Hand, C. K., & Rouleau, G. A. (2002) · Muscle & Nerve · doi:10.1002/mus.10001 · Cited by 235 · see citing works
Ince (1998) · doi:10.1046/j.1365-2990.1998.00108.x · Cited by 224 · see citing works
Malaspina, A., Kaushik, N. K., & de Belleroche, J. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.t01-1-00231.x · Cited by 212 · see citing works
Dorfin Ubiquitylates Mutant SOD1 and Prevents Mutant SOD1-mediated Neurotoxicity
Niwa, J.-I., Ishigaki, S., Hishikawa, N., Yamamoto, M., Doyu, M., Murata, S., Tanaka, K., Taniguchi, N., & Sobue, G. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m206559200 · Cited by 209 · see citing works
Self-citationHensley, K., Floyd, R. A., Gordon, B., Mou, S., Pye, Q. N., Stewart, C. A., West, M. S., & Williamson, K. S. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.00968.x · Cited by 200 · see citing works
Altered expression of bcl‐2 and bax mRNA in amyotrophic lateral sclerosis spinal cord motor neurons
Mu, X., He, J., Anderson, D. W., Springer, J. E., & Trojanowski, J. Q. (1996) · Annals of Neurology · doi:10.1002/ana.410400307 · Cited by 183 · see citing works
Apoptosis in amyotrophic lateral sclerosis: a review of the evidence
Sathasivam, S., Ince, P. G., & Shaw, P. J. (2001) · Neuropathology and Applied Neurobiology · doi:10.1046/j.0305-1846.2001.00332.x · Cited by 164 · see citing works
Alterations in G1 to S Phase Cell-Cycle Regulators during Amyotrophic Lateral Sclerosis
Ranganathan, S., & Bowser, R. P. (2003) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63879-5 · Cited by 160 · see citing works
Dangond, F., Hwang, D., Camelo, S. I., Pasinelli, P., Frosch, M. P., Stephanopoulos, G. N., Stephanopoulos, G., Brown, R. H., & Gullans, S. R. (2004) · Physiological Genomics · doi:10.1152/physiolgenomics.00087.2001 · Cited by 148 · see citing works
Mears, S. C., & Frank, E. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-09-03128.1997 · Cited by 132 · see citing works
Bunina bodies in amyotrophic lateral sclerosis immunostained with rabbit anti-cystatin C serum
Okamoto, K., Hirai, S., Amari, M., Watanabe, M., & Sakurai, A. (1993) · Neuroscience Letters · doi:10.1016/0304-3940(93)90576-7 · Cited by 127 · see citing works
Wang, J., Delabie, J., Aasheim, H., Smeland, E. B., & Myklebost, O. (2002) · BMC Bioinformatics · doi:10.1186/1471-2105-3-36 · Cited by 125 · see citing works
Sobue, G., Hashizume, Y., Yasuda, T., Mukai, E., Kumagai, T., Mitsuma, T., & Trojanowski, J. Q. (1990) · Acta Neuropathologica · doi:10.1007/bf00308716 · Cited by 121 · see citing works
Self-citationMicrobeam MOMeNT: non-contact laser microdissection of membrane-mounted native tissue.
Böhm, M., Wieland, I., Schütze, K., et al. (1997) · PubMed · Cited by 114 · see citing works
Kamei, Y., Inagaki, N., Nishizawa, M., Tsutsumi, O., Taketani, Y., & Inagaki, M. (1998) · Glia · doi:10.1002/(sici)1098-1136(199807)23:3 · Cited by 114 · see citing works
Acetylation Suppresses the Proapoptotic Activity of GD3 Ganglioside
Malisan, F., Franchi, L., Tomassini, B., Ventura, N., Condò, I., Rippo, M. R., Rufini, A., Liberati, L., Nachtigall, C., Kniep, B., et al. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20020960 · Cited by 114 · see citing works
Chen, H., Tourtellotte, W. G., & Frank, E. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-09-03512.2002 · Cited by 107 · see citing works
Kanamori, A., Nakayama, J., Fukuda, M. N., et al. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.7.2897 · Cited by 106 · see citing works
Upregulation of Bax protein and increased DNA degradation in ALS spinal cord motor neurons
Ekegren, T., Grundström, E., Lindholm, D., & Aquilonius, S. M. (2009) · Acta Neurologica Scandinavica · doi:10.1111/j.1600-0404.1999.tb00403.x · Cited by 91 · see citing works
[On intracellular inclusions in familial amyotrophic lateral sclerosis].
Tl, B. (1962) · PubMed · Cited by 88 · see citing works
Ideguchi, H., Ueda, A., Tanaka, M., Yang, J. H., Tsuji, T., Ohno, S., Hagiwara, E., Aoki, A., & Ishigatsubo, Y. (2002) · Biochemical Journal · doi:10.1042/bj20011851 · Cited by 87 · see citing works
Antoine, J.-C. G., Cinotti, L., Tilikete, C., Bouhour, F., Camdessanch�, J. P., Confavreux, C., Vighetto, A., Renault‐Mannel, V., Michel, D., & Honnorat, J. (2000) · Annals of Neurology · doi:10.1002/1531-8249(200007)48:1 · Cited by 86 · see citing works
Oxidative stress: its role in the pathogenesis of amyotrophic lateral sclerosis
Bergeron, C. (1995) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(95)00071-9 · Cited by 76 · see citing works
Kawahara, Y., Ito, K., Sun, H., Kanazawa, I., & Kwak, S. (2003) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2003.02718.x · Cited by 73 · see citing works
Farah, C. A., Nguyen, M. D., Julien, J., & Leclerc, N. M. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.01505.x · Cited by 64 · see citing works
Ganglioside patterns in amyotrophic lateral sclerosis brain regions
Rapport, M. M., Donnenfeld, H., Brunner, W., Hungund, B. L., & Bartfeld, H. (1985) · Annals of Neurology · doi:10.1002/ana.410180111 · Cited by 60 · see citing works
Terao, S.-I., Sobue, G., Hashizume, Y., et al. (1994) · Journal of Neurology · doi:10.1007/bf00863768 · Cited by 57 · see citing works
Self-citationDegenerating compartment and functioning compartment of motor neurons in ALS
Sobue, G., Sahashi, K., Takahashi, A., et al. (1983) · Neurology · doi:10.1212/wnl.33.5.654 · Cited by 57 · see citing works
Self-citationA Role of Midkine in the Development of the Neuromuscular Junction
Zhou, H., Muramatsu, T., Halfter, W. M., Tsim, K. W. K., & Peng, H. B. (1997) · Molecular and Cellular Neuroscience · doi:10.1006/mcne.1997.0638 · Cited by 55 · see citing works
Hishikawa, N., Niwa, J.-I., Doyu, M., Ito, T., Ishigaki, S., Hashizume, Y., & Sobue, G. (2003) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63688-7 · Cited by 54 · see citing works
Self-citationX‐Linked inhibitor of apoptosis protein is involved in mutant SOD1‐mediated neuronal degeneration
Ishigaki, S., Liang, Y., Yamamoto, M., Niwa, J., Ando, Y., Yoshihara, T., Takeuchi, H., Doyu, M., & Sobue, G. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.00998.x · Cited by 49 · see citing works
Self-citationLooking Beyond Morphology: Cancer Gene Expression Profiling Using DNA Microarrays
Luo, J., Isaacs, W. B., Trent, J. M., & Duggan, D. J. (2003) · Cancer Investigation · doi:10.1081/cnv-120025096 · Cited by 49 · see citing works
Colbert, M. C., Rubin, W. W., Linney, E. A., & LaMantia, A. (1995) · Developmental Dynamics · doi:10.1002/aja.1002040102 · Cited by 44 · see citing works
Yamamoto, M., Sobue, G., Yamamoto, K., et al. (1996) · Neuroscience Letters · doi:10.1016/0304-3940(96)12342-9 · Cited by 41 · see citing works
Self-citationWatanabe, H., Tanaka, F., Doyu, M., Riku, S., Yoshida, M., Hashizume, Y., & Sobue, G. (2000) · Human Genetics · doi:10.1007/s004390000400 · Cited by 38 · see citing works
Self-citationMalaspina, A., & de Belleroche, J. (2004) · Brain Research Reviews · doi:10.1016/j.brainresrev.2004.04.002 · Cited by 36 · see citing works
Absence of mutations in the hypoxia response element of VEGF in ALS
Gros‐Louis, F., Laurent, S. B., Lopes, A. A. S., et al. (2003) · Muscle & Nerve · doi:10.1002/mus.10498 · Cited by 34 · see citing works
Ando, Y., Liang, Y., Ishigaki, S., et al. (2003) · Neurochemical Research · doi:10.1023/a:1023258923002 · Cited by 22 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Mutations of optineurin in amyotrophic lateral sclerosis
Maruyama, H., Morino, H., Ito, H., Izumi, Y., Kato, H., Watanabe, Y., Kinoshita, Y., Kamada, M., Nodera, H., Suzuki, H., et al. (2010) · Nature · doi:10.1038/nature08971 · Cited by 1,265 · see citing works
Retinoic acid in the development, regeneration and maintenance of the nervous system
Maden, M. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2212 · Cited by 896 · see citing works
Diagnosis and management of motor neurone disease
McDermott, C. J., & Shaw, P. J. (2008) · BMJ · doi:10.1136/bmj.39493.511759.be · Cited by 220 · see citing works
Misregulated RNA processing in amyotrophic lateral sclerosis
Polymenidou, M., Lagier-Tourenne, C., Hutt, K. R., Bennett, C. F., Cleveland, D. W., & Yeo, G. W. (2012) · Brain Research · doi:10.1016/j.brainres.2012.02.059 · Cited by 169 · see citing works
The Complex Molecular Biology of Amyotrophic Lateral Sclerosis (ALS)
Redler, R. L., & Dokholyan, N. V. (2012) · Progress in Molecular Biology and Translational Science · doi:10.1016/b978-0-12-385883-2.00002-3 · Cited by 172 · see citing works
SQSTM1 mutations – Bridging Paget disease of bone and ALS/FTLD
Rea, S. L., Majcher, V., Searle, M. S., & Layfield, R. (2014) · Experimental Cell Research · doi:10.1016/j.yexcr.2014.01.020 · Cited by 152 · see citing works
La Barbera, L., Vedele, F., Nobili, A., Krashia, P., Spoleti, E., Latagliata, E. C., Cutuli, D., Cauzzi, E., Marino, R., Viscomi, M. T., et al. (2021) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2021.102031 · Cited by 98 · see citing works
Ubiquilin-2 drives NF-κB activity and cytosolic TDP-43 aggregation in neuronal cells
Picher-Martel, V., Dutta, K., Phaneuf, D., Sobue, G., & Julien, J.-P. (2015) · Molecular Brain · doi:10.1186/s13041-015-0162-6 · Cited by 65 · see citing works
Self-citationExpression profiling of drug response - from genes to pathways
Herwig, R., & Lehrach, H. (2006) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2006.8.3/rherwig · Cited by 14 · see citing works
Technology Insight: querying the genome with microarrays—progress and hope for neurological disease
Coppola, G., & Geschwind, D. H. (2006) · Nature Clinical Practice Neurology · doi:10.1038/ncpneuro0133 · Cited by 12 · see citing works
- Authors
- Jiang, Y., Yamamoto, M., Kobayashi, Y., Yoshihara, T., Liang, Y., Terao, S., Takeuchi, H., Ishigaki, S., Katsuno, M., Adachi, H., Niwa, J., Tanaka, F., Doyu, M., Yoshida, M., Hashizume, Y., & Sobue, G.
- Affiliations
- Nagoya University (JP)
- Aichi Medical University (JP)
- ORCID
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2005-01-24
- Volume
- 57
- Issue
- 2
- Pages
- 236-251
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- OpenAlex
- W2004508412
- Cited by
- 255
- References
- 53
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 7 · 2023: 9 · 2022: 13 · 2021: 6 · 2020: 7 · 2019: 7 · 2018: 8 · 2017: 9 · 2016: 12 · 2015: 8 · 2014: 12 · 2013: 13 · 2012: 20
- FWCI
- 13.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- 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
- sporadic ALS, spinal motoneurons, gene expression profiles, motor neuron degeneration, neuronal cell death, dynactin, microtubule-associated proteins, EGR3, axonal transport, neurotrophic factors, ciliary neurotrophic factor, hepatocyte growth factor, glial cell line-derived neurotrophic factor, NF-κB, caspases, neuroinflammation
- MeSH terms
- Adult, Aged, Aged, 80 and over, Amyotrophic Lateral Sclerosis, Anterior Horn Cells, Female, Humans, Immunohistochemistry, Lasers, Male, Middle Aged, Motor Neurons, Spinal Cord, In Situ Hybridization, DNA Primers, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Microdissection
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
