ArticleHuman molecular genetics2013
Amyotrophic lateral sclerosis-related VAPB P56S mutation differentially affects the function and survival of corticospinal and spinal motor neurons.
Article in Human molecular genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 42 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
42 citing papers in PubMed, 71 citations in OpenAlex.
- RHOA regulates mitochondria-ER contact sites through modulation of the VAPB/PTPIP51 tether.Nature communications · 2025Article
- Disclosing Pathogenic Variant Effects on the Structural Dynamics of the VAPB MSP Domain Causing Familial ALS.International journal of molecular sciences · 2025Article
- Preventing MSC aging and enhancing immunomodulation: Novel strategies for cell-based therapies.Regenerative therapy · 2025Review
- Pathogenic mechanisms of amyotrophic lateral sclerosis-linked VAPB P56S mutation in the degeneration of corticospinal motor neurons.Ageing and neurodegenerative diseases · 2025Article
- Spinal cord neurone loss and foot placement changes in a rat knock-in model of amyotrophic lateral sclerosis Type 8.Brain communications · 2024Article
- Article
- Autophagy Dysfunction in ALS: from Transport to Protein Degradation.Journal of molecular neuroscience : MN · 2022Review
- Modelling amyotrophic lateral sclerosis in rodents.Nature reviews. Neuroscience · 2022Review
- The Mechanism of Stem Cell Aging.Stem cell reviews and reports · 2022Review
- VAP Proteins - From Organelle Tethers to Pathogenic Host Interactors and Their Role in Neuronal Disease.Frontiers in cell and developmental biology · 2022Review
- Nearly 30 Years of Animal Models to Study Amyotrophic Lateral Sclerosis: A Historical Overview and Future Perspectives.International journal of molecular sciences · 2021Review
- Review
- Pathomechanisms of ALS8: altered autophagy and defective RNA binding protein (RBP) homeostasis due to the VAPB P56S mutation.Cell death & disease · 2021Article
- Protein disulfide isomerase ERp57 protects early muscle denervation in experimental ALS.Acta neuropathologica communications · 2021Article
- Proteomics-Based Approach Identifies Altered ER Domain Properties by ALS-Linked VAPB Mutation.Scientific reports · 2020Article
- Article
- Autophagy as a common pathway in amyotrophic lateral sclerosis.Neuroscience letters · 2019Review
- Transgenic and physiological mouse models give insights into different aspects of amyotrophic lateral sclerosis.Disease models & mechanisms · 2019Review
- A Systematic Review of Suggested Molecular Strata, Biomarkers and Their Tissue Sources in ALS.Frontiers in neurology · 2019Review
- Recent advances in understanding phosphoinositide signaling in the nervous system.F1000Research · 2019Review
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
The substitution of Proline with Serine at residue 56 (P56S) of vesicle-associated membrane protein-associated protein B (VAPB) has been linked to an atypical autosomal dominant form of familial amyotrophic lateral sclerosis 8 (ALS8). To investigate the pathogenic mechanism of P56S VAPB in ALS, we generated transgenic (Tg) mice that heterologously express human wild-type (WT) and P56S VAPB under the control of a pan-neuronal promoter Thy1.2. While WT VAPB Tg mice did not exhibit any overt motor behavioral phenotypes, P56S VAPB Tg mice developed progressive hyperactivities and other motor abnormalities. VAPB protein was accumulated as large punctate in the soma and proximal dendrites of both corticospinal motor neurons (CSMNs) and spinal motor neurons (SMNs) in P56S VAPB Tg mice. Concomitantly, a significant increase of endoplasmic reticulum stress and unfolded protein response and the resulting up-regulation of pro-apoptotic factor CCAAT/enhancer-binding protein homologous protein expression were observed in the CSMNs and SMNs of P56S VAPB Tg mice. However, only a progressive loss of CSMNs but not SMNs was found in P56S VAPB Tg mice. In SMNs, P56S VAPB promoted a rather selective translocation of VAPB protein onto the postsynaptic site of C-boutons that altered the morphology of C-boutons and impaired the spontaneous rhythmic discharges of SMNs. Therefore, these findings provide new pathophysiological mechanisms of P56S VAPB that differentially affect the function and survival of CSMNs and SMNs in ALS8.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.