ArticleBiology open2014
A genetic screen identifies Tor as an interactor of VAPB in a Drosophila model of amyotrophic lateral sclerosis.
Article in Biology open, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03359538 (Rapamycin), which is not on this map. Cited by 23 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Rapamycin (Sirolimus) Treatment for Amyotrophic Lateral Sclerosis
Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Meta-analysis of Genetic Modifiers Reveals Candidate Dysregulated Pathways in Amyotrophic Lateral Sclerosis.Neuroscience · 2019Pooled it
- Randomized, double-blind, placebo-controlled trial of rapamycin in amyotrophic lateral sclerosis.Nature communications · 2023Trial
- Trial
- Neuro-glial lipid imbalance in a Drosophila model of amyotrophic lateral sclerosis 8.Acta neuropathologica communications · 2026Article
- Fos regulates age-dependent neuroinflammation in a VAPP58S model of amyotrophic lateral sclerosis.Disease models & mechanisms · 2026Article
- Article
- The Drosophila tumour suppressor Lgl and Vap33 activate the Hippo pathway through a dual mechanism.Journal of cell science · 2024Article
- Therapeutic targeting of ALS pathways: Refocusing an incomplete picture.Annals of clinical and translational neurology · 2023Review
- 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
- 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
- Multifaceted roles of YEATS domain-containing proteins and novel links to neurological diseases.Cellular and molecular life sciences : CMLS · 2022Review
- Phenotypic heterogeneity in amyotrophic lateral sclerosis type 8 and modifying mechanisms of neurodegeneration.Neural regeneration research · 2021Article
- Amyotrophic Lateral Sclerosis and Frontotemporal Lobar Degenerations: Similarities in Genetic Background.Diagnostics (Basel, Switzerland) · 2021Review
- Amyotrophic Lateral Sclerosis: A Neurodegenerative Motor Neuron Disease With Ocular Involvement.Frontiers in neuroscience · 2020Review
- Canine Models of Inherited Musculoskeletal and Neurodegenerative Diseases.Frontiers in veterinary science · 2020Review
- SOD1 activity threshold and TOR signalling modulate VAP(P58S) aggregation via reactive oxygen species-induced proteasomal degradation in aDisease models & mechanisms · 2019Article
- Maximizing the Survival of Amyotrophic Lateral Sclerosis Patients: Current Perspectives.Neurology research international · 2018Review
- Protein Quality Control and the Amyotrophic Lateral Sclerosis/Frontotemporal Dementia Continuum.Frontiers in molecular neuroscience · 2017Article
- Inside out: the role of nucleocytoplasmic transport in ALS and FTLD.Acta neuropathologica · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder characterized by selective death of motor neurons. In 5-10% of the familial cases, the disease is inherited because of mutations. One such mutation, P56S, was identified in human VAPB that behaves in a dominant negative manner, sequestering wild type protein into cytoplasmic inclusions. We have conducted a reverse genetic screen to identify interactors of Drosophila VAPB. We screened 2635 genes and identified 103 interactors, of which 45 were enhancers and 58 were suppressors of VAPB function. Interestingly, the screen identified known ALS loci - TBPH, alsin2 and SOD1. Also identified were genes involved in cellular energetics and homeostasis which were used to build a gene regulatory network of VAPB modifiers. One key modifier identified was Tor, whose knockdown reversed the large bouton phenotype associated with VAP(P58S) expression in neurons. A similar reversal was seen by over-expressing Tuberous Sclerosis Complex (Tsc1,2) that negatively regulates TOR signaling as also by reduction of S6K activity. In comparison, the small bouton phenotype associated with VAP(wt) expression was reversed with Tsc1 knock down as well as S6K-CA expression. Tor therefore interacts with both VAP(wt) and VAP(P58S), but in a contrasting manner. Reversal of VAP(P58S) bouton phenotypes in larvae fed with the TOR inhibitor Rapamycin suggests upregulation of TOR signaling in response to VAP(P58S) expression. The VAPB network and further mechanistic understanding of interactions with key pathways, such as the TOR cassette, will pave the way for a better understanding of the mechanisms of onset and progression of motor neuron disease.
Indexed as
Identifiers
What OpenQuestion holds
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.