ArticleHuman molecular genetics2016
Neuronal overexpression of human VAPB slows motor impairment and neuromuscular denervation in a mouse model of ALS.
Article in Human molecular genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 27 citations in OpenAlex.
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- What the VAP: The Expanded VAP Family of Proteins Interacting With FFAT and FFAT-Related Motifs for Interorganellar Contact.Contact (Thousand Oaks (Ventura County, Calif.)) · 2021Article
- Examining the relationship between astrocyte dysfunction and neurodegeneration in ALS using hiPSCs.Neurobiology of disease · 2019Review
- The VAPB-PTPIP51 endoplasmic reticulum-mitochondria tethering proteins are present in neuronal synapses and regulate synaptic activity.Acta neuropathologica communications · 2019Article
- SOD1 activity threshold and TOR signalling modulate VAP(P58S) aggregation via reactive oxygen species-induced proteasomal degradation in aDisease models & mechanisms · 2019Article
- Disruption of ER-mitochondria signalling in fronto-temporal dementia and related amyotrophic lateral sclerosis.Cell death & disease · 2018Review
- Neurobiology of axonal transport defects in motor neuron diseases: Opportunities for translational research?Neurobiology of disease · 2017Review
- Interaction of Mitochondria with the Endoplasmic Reticulum and Plasma Membrane in Calcium Homeostasis, Lipid Trafficking and Mitochondrial Structure.International journal of molecular sciences · 2017Review
- Protein Homeostasis in Amyotrophic Lateral Sclerosis: Therapeutic Opportunities?Frontiers in molecular neuroscience · 2017Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Four mutations in the VAMP/synaptobrevin-associated protein B (VAPB) gene have been linked to amyotrophic lateral sclerosis (ALS) type 8. The mechanism by which VAPB mutations cause motor neuron disease is unclear, but studies of the most common P56S variant suggest both loss of function and dominant-negative sequestration of wild-type protein. Diminished levels of VAPB and its proteolytic cleavage fragment have also been reported in sporadic ALS cases, suggesting that VAPB loss of function may be a common mechanism of disease. Here, we tested whether neuronal overexpression of wild-type human VAPB would attenuate disease in a mouse model of familial ALS1. We used neonatal intraventricular viral injections to express VAPB or YFP throughout the brain and spinal cord of superoxide dismutase (SOD1) G93A transgenic mice. Lifelong elevation of neuronal VAPB slowed the decline of neurological impairment, delayed denervation of hindlimb muscles, and prolonged survival of spinal motor neurons. Collectively, these changes produced a slight but significant extension in lifespan, even in this highly aggressive model of disease. Our findings lend support for a protective role of VAPB in neuromuscular health.
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