Cited by 616Amyotrophic Lateral Sclerosis ResearchHereditary Neurological DisordersAlzheimer's disease research and treatments

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Molecular pathways of motor neuron injury in amyotrophic lateral sclerosis

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Ferraiuolo, Laura, Kirby, Janine, Grierson, Andrew J., Sendtner, Michael, Shaw, Pamela J.·2011·Nature Reviews Neurology

DOI 10.1038/nrneurol.2011.152

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Abstract

Amyotrophic lateral sclerosis (ALS) is a genetically diverse disease. At least 15 ALS-associated gene loci have so far been identified, and the causative gene is known in approximately 30% of familial ALS cases. Less is known about the factors underlying the sporadic form of the disease. The molecular mechanisms of motor neuron degeneration are best understood in the subtype of disease caused by mutations in superoxide dismutase 1, with a current consensus that motor neuron injury is caused by a complex interplay between multiple pathogenic processes. A key recent finding is that mutated TAR DNA-binding protein 43 is a major constituent of the ubiquitinated protein inclusions in ALS, providing a possible link between the genetic mutation and the cellular pathology. New insights have also indicated the importance of dysregulated glial cell-motor neuron crosstalk, and have highlighted the vulnerability of the distal axonal compartment early in the disease course. In addition, recent studies have suggested that disordered RNA processing is likely to represent a major contributing factor to motor neuron disease. Ongoing research on the cellular pathways highlighted in this Review is predicted to open the door to new therapeutic interventions to slow disease progression in ALS.

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Induction of the Unfolded Protein Response in Familial Amyotrophic Lateral Sclerosis and Association of Protein-disulfide Isomerase with Superoxide Dismutase 1
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Additional file 10 of SRSF1-dependent inhibition of C9ORF72-repeat RNA nuclear export: genome-wide mechanisms for neuroprotection in amyotrophic lateral sclerosis
Castelli, L. M., Cutillo, L., Souza, C. D. S., Sánchez-Martínez, Á., Granata, I., Lin, Y.-H., Myszczynska, M. A., Heath, P. R., Livesey, M. R., Ning, K., et al. (2021) · Figshare · doi:10.6084/m9.figshare.15145929
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Additional file 8 of SRSF1-dependent inhibition of C9ORF72-repeat RNA nuclear export: genome-wide mechanisms for neuroprotection in amyotrophic lateral sclerosis
Castelli, L. M., Cutillo, L., Souza, C. D. S., Sánchez-Martínez, Á., Granata, I., Lin, Y.-H., Myszczynska, M. A., Heath, P. R., Livesey, M. R., Ning, K., et al. (2021) · Figshare · doi:10.6084/m9.figshare.15145995
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Additional file 19 of SRSF1-dependent inhibition of C9ORF72-repeat RNA nuclear export: genome-wide mechanisms for neuroprotection in amyotrophic lateral sclerosis
Castelli, L. M., Cutillo, L., Souza, C. D. S., Sánchez-Martínez, Á., Granata, I., Lin, Y.-H., Myszczynska, M. A., Heath, P. R., Livesey, M. R., Ning, K., et al. (2021) · Figshare · doi:10.6084/m9.figshare.15145956
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Additional file 1 of SRSF1-dependent inhibition of C9ORF72-repeat RNA nuclear export: genome-wide mechanisms for neuroprotection in amyotrophic lateral sclerosis
Castelli, L. M., Cutillo, L., Souza, C. D. S., Sánchez-Martínez, Á., Granata, I., Lin, Y.-H., Myszczynska, M. A., Heath, P. R., Livesey, M. R., Ning, K., et al. (2021) · Figshare · doi:10.6084/m9.figshare.15145959
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Additional file 22 of SRSF1-dependent inhibition of C9ORF72-repeat RNA nuclear export: genome-wide mechanisms for neuroprotection in amyotrophic lateral sclerosis
Castelli, L. M., Cutillo, L., Souza, C. D. S., Sánchez-Martínez, Á., Granata, I., Lin, Y.-H., Myszczynska, M. A., Heath, P. R., Livesey, M. R., Ning, K., et al. (2021) · Figshare · doi:10.6084/m9.figshare.15145968
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Additional file 1 of Pathological characteristics of axons and alterations of proteomic and lipidomic profiles in midbrain dopaminergic neurodegeneration induced by WDR45-deficiency
Wang, P., Shao, Y., Al-Nusaif, M., Zhang, J., Yang, H., Yang, Y., Kim, K., Li, S., Liu, C., Cai, H., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26943114
Additional file 12 of SRSF1-dependent inhibition of C9ORF72-repeat RNA nuclear export: genome-wide mechanisms for neuroprotection in amyotrophic lateral sclerosis
Castelli, L. M., Cutillo, L., Souza, C. D. S., Sánchez-Martínez, Á., Granata, I., Lin, Y.-H., Myszczynska, M. A., Heath, P. R., Livesey, M. R., Ning, K., et al. (2021) · Figshare · doi:10.6084/m9.figshare.15145935
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Additional file 16 of SRSF1-dependent inhibition of C9ORF72-repeat RNA nuclear export: genome-wide mechanisms for neuroprotection in amyotrophic lateral sclerosis
Castelli, L. M., Cutillo, L., Souza, C. D. S., Sánchez-Martínez, Á., Granata, I., Lin, Y.-H., Myszczynska, M. A., Heath, P. R., Livesey, M. R., Ning, K., et al. (2021) · Figshare · doi:10.6084/m9.figshare.15145947
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Additional file 21 of SRSF1-dependent inhibition of C9ORF72-repeat RNA nuclear export: genome-wide mechanisms for neuroprotection in amyotrophic lateral sclerosis
Castelli, L. M., Cutillo, L., Souza, C. D. S., Sánchez-Martínez, Á., Granata, I., Lin, Y.-H., Myszczynska, M. A., Heath, P. R., Livesey, M. R., Ning, K., et al. (2021) · Figshare · doi:10.6084/m9.figshare.15145965
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Additional file 2 of Pathological characteristics of axons and alterations of proteomic and lipidomic profiles in midbrain dopaminergic neurodegeneration induced by WDR45-deficiency
Wang, P., Shao, Y., Al-Nusaif, M., Zhang, J., Yang, H., Yang, Y., Kim, K., Li, S., Liu, C., Cai, H., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26943117
Additional file 3 of Pathological characteristics of axons and alterations of proteomic and lipidomic profiles in midbrain dopaminergic neurodegeneration induced by WDR45-deficiency
Wang, P., Shao, Y., Al-Nusaif, M., Zhang, J., Yang, H., Yang, Y., Kim, K., Li, S., Liu, C., Cai, H., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26943120
Additional file 20 of SRSF1-dependent inhibition of C9ORF72-repeat RNA nuclear export: genome-wide mechanisms for neuroprotection in amyotrophic lateral sclerosis
Castelli, L. M., Cutillo, L., Souza, C. D. S., Sánchez-Martínez, Á., Granata, I., Lin, Y.-H., Myszczynska, M. A., Heath, P. R., Livesey, M. R., Ning, K., et al. (2021) · Figshare · doi:10.6084/m9.figshare.15145962
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Additional file 23 of SRSF1-dependent inhibition of C9ORF72-repeat RNA nuclear export: genome-wide mechanisms for neuroprotection in amyotrophic lateral sclerosis
Castelli, L. M., Cutillo, L., Souza, C. D. S., Sánchez-Martínez, Á., Granata, I., Lin, Y.-H., Myszczynska, M. A., Heath, P. R., Livesey, M. R., Ning, K., et al. (2021) · Figshare · doi:10.6084/m9.figshare.15145971
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Additional file 15 of SRSF1-dependent inhibition of C9ORF72-repeat RNA nuclear export: genome-wide mechanisms for neuroprotection in amyotrophic lateral sclerosis
Castelli, L. M., Cutillo, L., Souza, C. D. S., Sánchez-Martínez, Á., Granata, I., Lin, Y.-H., Myszczynska, M. A., Heath, P. R., Livesey, M. R., Ning, K., et al. (2021) · Figshare · doi:10.6084/m9.figshare.15145944
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Additional file 24 of SRSF1-dependent inhibition of C9ORF72-repeat RNA nuclear export: genome-wide mechanisms for neuroprotection in amyotrophic lateral sclerosis
Castelli, L. M., Cutillo, L., Souza, C. D. S., Sánchez-Martínez, Á., Granata, I., Lin, Y.-H., Myszczynska, M. A., Heath, P. R., Livesey, M. R., Ning, K., et al. (2021) · Figshare · doi:10.6084/m9.figshare.15145974
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Authors: Ferraiuolo, L., Kirby, J., Grierson, A. J., Sendtner, M., & Shaw, P. J.
Affiliations: University of Sheffield (GB)
University of Würzburg (DE)
Corresponding author: Shaw, Pamela J.
ORCID: Ferraiuolo, Laura
Kirby, Janine
Grierson, Andrew J.
Sendtner, Michael
Shaw, Pamela J.
Venue: Nature Reviews Neurology
Publisher: Springer Science and Business Media LLC
Published: 2011-11
Volume: 7
Issue: 11
Pages: 616-630
ISSN: 1759-4758 (ISSN-L)
1759-4766
DOI: 10.1038/nrneurol.2011.152
OpenAlex: W2025413109
Cited by: 615
References: 202
Citations by year: 2026: 12 · 2025: 24 · 2024: 34 · 2023: 25 · 2022: 27 · 2021: 54 · 2020: 34 · 2019: 37 · 2018: 33 · 2017: 42 · 2016: 58 · 2015: 63 · 2014: 63 · 2013: 64 · 2012: 45
FWCI: 6.83
Type: journal article
Language: en
Open access: green
zenodo.org
Licence: other-oa
www.springer.com/tdm (tdm)
Locations: Nature Reviews Neurology (publishedVersion)
PubMed (publishedVersion)
Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, other-oa)
Funders: Wellcome Trust
Topics: Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Keywords: amyotrophic lateral sclerosis, motor neuron injury, motor neuron degeneration, oxidative stress, mitochondrial dysfunction, excitotoxicity, superoxide dismutase 1, TDP-43, sporadic ALS, familial ALS, therapeutic target
MeSH terms: Amyotrophic Lateral Sclerosis, Humans, Motor Neurons, Nerve Degeneration

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Molecular pathways of motor neuron injury in amyotrophic lateral sclerosis

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