ArticleBiology open2014
Gain-of-function mutations in the ALS8 causative gene VAPB have detrimental effects on neurons and muscles.
Article in Biology open, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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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.
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Who cites it
22 citing papers in PubMed, 36 citations in OpenAlex.
- Neuro-glial lipid imbalance in a Drosophila model of amyotrophic lateral sclerosis 8.Acta neuropathologica communications · 2026Article
- Catalytic activity of the Bin3/MePCE methyltransferase domain is dispensable for 7SK snRNP function in Drosophila melanogaster.Genetics · 2024Article
- Overexpression of mTOR in Leukocytes from ALS8 Patients.Current neuropharmacology · 2023Article
- Loss of Activity-Induced Mitochondrial ATP Production Underlies the Synaptic Defects in aThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Autophagy Dysfunction in ALS: from Transport to Protein Degradation.Journal of molecular neuroscience : MN · 2022Review
- Intellectual disability-associated disruption of O-GlcNAc cycling impairs habituation learning in Drosophila.PLoS genetics · 2022Article
- VAP Proteins - From Organelle Tethers to Pathogenic Host Interactors and Their Role in Neuronal Disease.Frontiers in cell and developmental biology · 2022Review
- Review
- Disruption of Tip60 HAT mediated neural histone acetylation homeostasis is an early common event in neurodegenerative diseases.Scientific reports · 2020Article
- ALS Genetics, Mechanisms, and Therapeutics: Where Are We Now?Frontiers in neuroscience · 2019Review
- Genetics of Amyotrophic Lateral Sclerosis.Cold Spring Harbor perspectives in medicine · 2018Review
- A postsynaptic PI3K-cII dependent signaling controller for presynaptic homeostatic plasticity.eLife · 2018Article
- ALS-Associated Endoplasmic Reticulum Proteins in Denervated Skeletal Muscle: Implications for Motor Neuron Disease Pathology.Brain pathology (Zurich, Switzerland) · 2017Article
- Protein Quality Control and the Amyotrophic Lateral Sclerosis/Frontotemporal Dementia Continuum.Frontiers in molecular neuroscience · 2017Article
- Why Quantification Matters: Characterization of Phenotypes at the Drosophila Larval Neuromuscular Junction.Journal of visualized experiments : JoVE · 2016Article
- VAMP-associated Proteins (VAP) as Receptors That Couple Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Proteostasis with Lipid Homeostasis.The Journal of biological chemistry · 2016Article
- Adducin at the Neuromuscular Junction in Amyotrophic Lateral Sclerosis: Hanging on for Dear Life.Frontiers in cellular neuroscience · 2016Review
- A systematic screening to identify de novo mutations causing sporadic early-onset Parkinson's disease.Human molecular genetics · 2015Article
- Review
- A fruitful endeavor: modeling ALS in the fruit fly.Brain research · 2015Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Amyotrophic Lateral Sclerosis (ALS) is a motor neuron degenerative disease characterized by a progressive, and ultimately fatal, muscle paralysis. The human VAMP-Associated Protein B (hVAPB) is the causative gene of ALS type 8. Previous studies have shown that a loss-of-function mechanism is responsible for VAPB-induced ALS. Recently, a novel mutation in hVAPB (V234I) has been identified but its pathogenic potential has not been assessed. We found that neuronal expression of the V234I mutant allele in Drosophila (DVAP-V260I) induces defects in synaptic structure and microtubule architecture that are opposite to those associated with DVAP mutants and transgenic expression of other ALS-linked alleles. Expression of DVAP-V260I also induces aggregate formation, reduced viability, wing postural defects, abnormal locomotion behavior, nuclear abnormalities, neurodegeneration and upregulation of the heat-shock-mediated stress response. Similar, albeit milder, phenotypes are associated with the overexpression of the wild-type protein. These data show that overexpressing the wild-type DVAP is sufficient to induce the disease and that DVAP-V260I is a pathogenic allele with increased wild-type activity. We propose that a combination of gain- and loss-of-function mechanisms is responsible for VAPB-induced ALS.
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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.