The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
Characterization of the Properties of a Novel Mutation in VAPB in Familial Amyotrophic Lateral Sclerosis
Open accessAbstract
Following the mutation screening of genes known to cause amyotrophic lateral sclerosis (ALS) in index cases from 107 familial ALS (FALS) kindred, a point mutation was identified in vesicle-associated membrane protein-associated protein B (VAPB), or VAMP-associated protein B, causing an amino acid change from threonine to isoleucine at codon 46 (T46I) in one FALS case but not in 257 controls. This is an important finding because it is only the second mutation identified in this gene that causes ALS. In order to investigate the pathogenic effects of this mutation, we have used a motor neuron cell line and tissue-specific expression of the mutant protein in Drosophila. We provide substantial evidence for the pathogenic effects of this mutation in abolishing the effect of wild type VAPB in the unfolded protein response, promoting ubiquitin aggregate formation, and activating neuronal cell death. We also report that expression of the mutant protein in the Drosophila motor system induces aggregate deposition, endoplasmic reticulum disorganization, and chaperone up-regulation both in neurons and in muscles. Our integrated analysis of the pathogenic effect of the T46I mutation and the previously identified P56S mutation indicate extensive commonalities in the disease mechanism for these two mutations. In summary, we show that this newly identified mutation in human FALS has a pathogenic effect, supporting and reinforcing the role of VAPB as a causative gene of ALS.
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Mutations of optineurin in amyotrophic lateral sclerosis
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Molecular biology of amyotrophic lateral sclerosis: insights from genetics
Pasinelli, P., & Brown, R. H. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1971 · Cited by 1,107
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Tauopathy in Drosophila : Neurodegeneration Without Neurofibrillary Tangles
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Extracellular mutant SOD1 induces microglial‐mediated motoneuron injury
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Cited by
Decoding ALS: from genes to mechanism
Taylor, J. P., Brown, R. H., & Cleveland, D. W. (2016) · Nature · doi:10.1038/nature20413 · Cited by 2,066
Converging Mechanisms in ALS and FTD: Disrupted RNA and Protein Homeostasis
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Endoplasmic reticulum stress signalling-from basic mechanisms to clinical applications
Almanza, A., Carlesso, A., Chintha, C., Creedican, S., Doultsinos, D., Leuzzi, B., Luís, A., McCarthy, N., Montibeller, L., More, S., et al. (2019) · The FEBS Journal · doi:10.1111/febs.14608 · Cited by 1,034
Self-citationClinical genetics of amyotrophic lateral sclerosis: what do we really know?
Andersen, P. M., & Al-Chalabi, A. (2011) · Nature Reviews Neurology · doi:10.1038/nrneurol.2011.150 · Cited by 687
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
Metadata
- Authors
- Chen, H.-J., Anagnostou, G., Chai, A., Withers, J., Morris, A., Adhikaree, J., Pennetta, G., & de Belleroche, J. S.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2010-12
- Volume
- 285
- Issue
- 51
- Pages
- 40266-40281
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2117168196
- Cited by
- 189
- References
- 8
- FWCI
- 9.72
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- The paper
- Chen, H.-J., Anagnostou, G., Chai, A., Withers, J., Morris, A., Adhikaree, J., Pennetta, G., & de Belleroche, J. S. (2010). Characterization of the Properties of a Novel Mutation in VAPB in Familial Amyotrophic Lateral Sclerosis. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m110.161398
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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