ArticleNature chemical biology2011
A screen for regulators of survival of motor neuron protein levels.
Article in Nature chemical biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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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
45 citing papers in PubMed, 89 citations in OpenAlex.
- Evaluation of the orally bioavailable 4-phenylbutyrate-tethered trichostatin A analogue AR42 in models of spinal muscular atrophy.Scientific reports · 2023Article
- Spinal Cord Organoids to Study Motor Neuron Development and Disease.Life (Basel, Switzerland) · 2023Review
- Regulation of Survival Motor Neuron Gene Expression by Calcium Signaling.International journal of molecular sciences · 2021Article
- Combining multiomics and drug perturbation profiles to identify muscle-specific treatments for spinal muscular atrophy.JCI insight · 2021Article
- RNA-Targeting Splicing Modifiers: Drug Development and Screening Assays.Molecules (Basel, Switzerland) · 2021Review
- Article
- Pro-myogenic small molecules revealed by a chemical screen on primary muscle stem cells.Skeletal muscle · 2020Article
- Drug Screening and Drug Repositioning as Promising Therapeutic Approaches for Spinal Muscular Atrophy Treatment.Frontiers in pharmacology · 2020Review
- Applying Deep Neural Network Analysis to High-Content Image-Based Assays.SLAS discovery : advancing life sciences R & D · 2019Article
- Screening-Based Chemical Approaches to Unravel Stem Cell Biology.Stem cell reports · 2018Review
- Blocking p62-dependent SMN degradation ameliorates spinal muscular atrophy disease phenotypes.The Journal of clinical investigation · 2018Article
- Mechanistic studies of a small-molecule modulator of SMN2 splicing.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Self-oligomerization regulates stability of survival motor neuron protein isoforms by sequestering an SCFMolecular biology of the cell · 2018Article
- Axon outgrowth and neuronal differentiation defects after a-SMN and FL-SMN silencing in primary hippocampal cultures.PloS one · 2018Article
- Article
- A neuroprotective agent that inactivates prodegenerative TrkA and preserves mitochondria.The Journal of cell biology · 2017Article
- UsnRNP biogenesis: mechanisms and regulation.Chromosoma · 2017Review
- Article
- Studying human disease using human neurons.Brain research · 2017Review
- Small Molecules in Development for the Treatment of Spinal Muscular Atrophy.Journal of medicinal chemistry · 2016Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
The motor neuron disease spinal muscular atrophy (SMA) results from mutations that lead to low levels of the ubiquitously expressed protein survival of motor neuron (SMN). An ever-increasing collection of data suggests that therapeutics that elevate SMN may be effective in treating SMA. We executed an image-based screen of annotated chemical libraries and discovered several classes of compounds that were able to increase cellular SMN. Among the most important was the RTK-PI3K-AKT-GSK-3 signaling cascade. Chemical inhibitors of glycogen synthase kinase 3 (GSK-3) and short hairpin RNAs (shRNAs) directed against this target elevated SMN levels primarily by stabilizing the protein. It was particularly notable that GSK-3 chemical inhibitors were also effective in motor neurons, not only in elevating SMN levels, but also in blocking the death that was produced when SMN was acutely reduced by an SMN-specific shRNA. Thus, we have established a screen capable of detecting drug-like compounds that correct the main phenotypic change underlying SMA.
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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.