ArticleMolecular therapy : the journal of the American Society of Gene Therapy2019
A Stem Cell-Based Screening Platform Identifies Compounds that Desensitize Motor Neurons to Endoplasmic Reticulum Stress.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05279755 (A Phase 1, Randomized, Double-Blind, Placebo-Controlled Dose Escalating Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single Ascending and Multiple Ascending Doses of Prosetin in Healthy Volunteers and Participants With Amyotrophic Lateral Sclerosis), which is not on this map. Cited by 30 papers.
What it found
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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.
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.
A Phase 1, Randomized, Double-Blind, Placebo-Controlled Dose Escalating Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single Ascending and Multiple Ascending Doses of Prosetin in Healthy Volunteers and Participants With Amyotrophic Lateral Sclerosis (ALS) With an Optional Open-Label Extended Treatment Period for ALS Participants Who Complete 14 Days of Blinded Treatment
Who cites it
30 citing papers in PubMed, 51 citations in OpenAlex.
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- The motor neuron m6A repertoire governs neuronal homeostasis and FTO inhibition mitigates ALS symptom manifestation.Nature communications · 2025Article
- Swift induction of human spinal lower motor neurons and robust ALS cell screening via single-cell imaging.Stem cell reports · 2025Article
- Altered mitochondria-associated ER membrane (MAM) function shifts mitochondrial metabolism in amyotrophic lateral sclerosis (ALS).Nature communications · 2025Article
- Emerging Roles of Bile Acids and TGR5 in the Central Nervous System: Molecular Functions and Therapeutic Implications.International journal of molecular sciences · 2024Review
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- Microbiota-gut-brain axis and its therapeutic applications in neurodegenerative diseases.Signal transduction and targeted therapy · 2024Review
- Screens in aging-relevant human ALS-motor neurons identify MAP4Ks as therapeutic targets for the disease.Cell death & disease · 2024Article
- Protein aggregation and therapeutic strategies in SOD1- and TDP-43- linked ALS.Frontiers in molecular biosciences · 2024Review
- Tauroursodeoxycholic acid: a bile acid that may be used for the prevention and treatment of Alzheimer's disease.Frontiers in neuroscience · 2024Review
- Tauro-Urso-Deoxycholic Acid Trials in Amyotrophic Lateral Sclerosis: What is Achieved and What to Expect.Clinical drug investigation · 2023Review
- Small molecules targeting different cellular pathologies for the treatment of amyotrophic lateral sclerosis.Medicinal research reviews · 2023Review
- Analysis of proteome-wide degradation dynamics in ALS SOD1 iPSC-derived patient neurons reveals disrupted VCP homeostasis.Cell reports · 2023Article
- Nutritional and metabolic factors in amyotrophic lateral sclerosis.Nature reviews. Neurology · 2023Review
- Stem cell-derived brainstem mouse astrocytes obtain a neurotoxic phenotype in vitro upon neuroinflammation.Journal of inflammation (London, England) · 2023Article
- Roles of bile acids signaling in neuromodulation under physiological and pathological conditions.Cell & bioscience · 2023Review
- Discovery of a Potent and Selective CDKL5/GSK3 Chemical Probe That Is Neuroprotective.ACS chemical neuroscience · 2023Article
- A Potent and Selective CDKL5/GSK3 Chemical Probe is Neuroprotective.bioRxiv : the preprint server for biology · 2023Article
- Bile Acids Induce Neurite Outgrowth in Nsc-34 Cells via TGR5 and a Distinct Transcriptional Profile.Pharmaceuticals (Basel, Switzerland) · 2023Article
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease selectively targeting motor neurons in the brain and spinal cord. The reasons for differential motor neuron susceptibility remain elusive. We developed a stem cell-based motor neuron assay to study cell-autonomous mechanisms causing motor neuron degeneration, with implications for ALS. A small-molecule screen identified cyclopiazonic acid (CPA) as a stressor to which stem cell-derived motor neurons were more sensitive than interneurons. CPA induced endoplasmic reticulum stress and the unfolded protein response. Furthermore, CPA resulted in an accelerated degeneration of motor neurons expressing human superoxide dismutase 1 (hSOD1) carrying the ALS-causing G93A mutation, compared to motor neurons expressing wild-type hSOD1. A secondary screen identified compounds that alleviated CPA-mediated motor neuron degeneration: three kinase inhibitors and tauroursodeoxycholic acid (TUDCA), a bile acid derivative. The neuroprotective effects of these compounds were validated in human stem cell-derived motor neurons carrying a mutated SOD1 allele (hSOD1
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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.