ArticleHuman molecular genetics2015
Vapb/Amyotrophic lateral sclerosis 8 knock-in mice display slowly progressive motor behavior defects accompanying ER stress and autophagic response.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 52 citations in OpenAlex.
- VAPB confers selective neuroprotection by driving autophagic degradation of pathogenic aggregates in ALS.Acta neuropathologica communications · 2026Article
- Disclosing Pathogenic Variant Effects on the Structural Dynamics of the VAPB MSP Domain Causing Familial ALS.International journal of molecular sciences · 2025Article
- A role for mitochondria-ER crosstalk in amyotrophic lateral sclerosis 8 pathogenesis.Life science alliance · 2025Article
- Artificial enforcement of the unfolded protein response reduces disease features in multiple preclinical models of ALS/FTD.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Review
- The role of autophagy in the pathogenesis and treatment of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).Autophagy reports · 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
- The endolysosomal pathway and ALS/FTD.Trends in neurosciences · 2023Review
- VAPB-mediated ER-targeting stabilizes IRS-1 signalosomes to regulate insulin/IGF signaling.Cell discovery · 2023Article
- Endoplasmic Reticulum Membrane Contact Sites, Lipid Transport, and Neurodegeneration.Cold Spring Harbor perspectives in biology · 2023Review
- Caspar, an adapter for VAPB and TER94, modulates the progression of ALS8 by regulating IMD/NFκB-mediated glial inflammation in a Drosophila model of human disease.Human molecular genetics · 2022Article
- 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
- VAP Proteins - From Organelle Tethers to Pathogenic Host Interactors and Their Role in Neuronal Disease.Frontiers in cell and developmental biology · 2022Review
- The Interplay Between Autophagy and RNA Homeostasis: Implications for Amyotrophic Lateral Sclerosis and Frontotemporal Dementia.Frontiers in cell and developmental biology · 2022Review
- Sequestosome 1 Is Part of the Interaction Network of VAPB.International journal of molecular sciences · 2021Article
- 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
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Missense mutations (P56S) in Vapb are associated with autosomal dominant motor neuron diseases: amyotrophic lateral sclerosis and lower motor neuron disease. Although transgenic mice overexpressing the mutant vesicle-associated membrane protein-associated protein B (VAPB) protein with neuron-specific promoters have provided some insight into the toxic properties of the mutant proteins, their role in pathogenesis remains unclear. To identify pathological defects in animals expressing the P56S mutant VAPB protein at physiological levels in the appropriate tissues, we have generated Vapb knock-in mice replacing wild-type Vapb gene with P56S mutant Vapb gene and analyzed the resulting pathological phenotypes. Heterozygous P56S Vapb knock-in mice show mild age-dependent defects in motor behaviors as characteristic features of the disease. The homozygous P56S Vapb knock-in mice show more severe defects compared with heterozygous mice reflecting the dominant and dose-dependent effects of P56S mutation. Significantly, the knock-in mice demonstrate accumulation of P56S VAPB protein and ubiquitinated proteins in cytoplasmic inclusions, selectively in motor neurons. The mutant mice demonstrate induction of ER stress and autophagic response in motor neurons before obvious onset of behavioral defects, suggesting that these cellular biological defects might contribute to the initiation of the disease. The P56S Vapb knock-in mice could be a valuable tool to gain a better understanding of the mechanisms by which the disease arises.
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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.