ArticleCell reports2021
Human amyotrophic lateral sclerosis excitability phenotype screen: Target discovery and validation.
Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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Who cites it
27 citing papers in PubMed, 59 citations in OpenAlex.
- Large-scale drug screening in iPSC-derived motor neurons from sporadic ALS patients identifies a potential combinatorial therapy.Nature neuroscience · 2026Article
- Dynamic changes in excitability and viability of sporadic andFrontiers in cell and developmental biology · 2026Article
- Neuronal activity-dependent gene dysregulation inAmerican journal of physiology. Cell physiology · 2025Article
- Ropinirole Functions Through a Dopamine Receptor D2-Independent Mechanism to Ameliorate Amyotrophic Lateral Sclerosis Phenotypes in TARDBP-Mutant iPSC-Derived Motor Neurons.Journal of neurochemistry · 2025Article
- An organ-chip model of sporadic ALS using iPSC-derived spinal cord motor neurons and an integrated blood-brain-like barrier.Cell stem cell · 2025Article
- Polyethyleneimine facilitates the growth and electrophysiological characterization of iPSC-derived motor neurons.Scientific reports · 2024Article
- How is Excitotoxicity Being Modelled in iPSC-Derived Neurons?Neurotoxicity research · 2024Review
- Cell therapy for neurological disorders.Nature medicine · 2024Review
- ALS-associated C21ORF2 variant disrupts DNA damage repair, mitochondrial metabolism, neuronal excitability and NEK1 levels in human motor neurons.Acta neuropathologica communications · 2024Article
- Advances in Brain Stimulation, Nanomedicine and the Use of Magnetoelectric Nanoparticles: Dopaminergic Alterations and Their Role in Neurodegeneration and Drug Addiction.Molecules (Basel, Switzerland) · 2024Review
- A small-molecule activation mechanism that directly opens the KCNQ2 channel.Nature chemical biology · 2024Article
- Article
- Pathophysiology of ion channels in amyotrophic lateral sclerosis.Molecular brain · 2023Review
- Intranasal neuropeptide Y1 receptor antagonism improves motor deficits in symptomatic SOD1 ALS mice.Annals of clinical and translational neurology · 2023Article
- Small molecules targeting different cellular pathologies for the treatment of amyotrophic lateral sclerosis.Medicinal research reviews · 2023Review
- Seeing Neurodegeneration in a New Light Using Genetically Encoded Fluorescent Biosensors and iPSCs.International journal of molecular sciences · 2023Review
- Phenotypic screening using waveform analysis of synchronized calcium oscillations in primary cortical cultures.PloS one · 2023Article
- Molecular Identification of Pro-Excitogenic Receptor and Channel Phenotypes of the Deafferented Lumbar Motoneurons in the Early Phase after SCT in Rats.International journal of molecular sciences · 2022Article
- Is Dutasteride a Therapeutic Alternative for Amyotrophic Lateral Sclerosis?Biomedicines · 2022Review
- Melatonin Induces Autophagy in Amyotrophic Lateral Sclerosis Mice via Upregulation of SIRT1.Molecular neurobiology · 2022Article
Corrections and comments
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Authors and funding
24 authors at 5 institutions in 1 country.
Funding
Abstract
Drug development is hampered by poor target selection. Phenotypic screens using neurons differentiated from patient stem cells offer the possibility to validate known and discover novel disease targets in an unbiased fashion. To identify targets for managing hyperexcitability, a pathological feature of amyotrophic lateral sclerosis (ALS), we design a multi-step screening funnel using patient-derived motor neurons. High-content live cell imaging is used to evaluate neuronal excitability, and from a screen against a chemogenomic library of 2,899 target-annotated compounds, 67 reduce the hyperexcitability of ALS motor neurons carrying the SOD1(A4V) mutation, without cytotoxicity. Bioinformatic deconvolution identifies 13 targets that modulate motor neuron excitability, including two known ALS excitability modulators, AMPA receptors and Kv7.2/3 ion channels, constituting target validation. We also identify D2 dopamine receptors as modulators of ALS motor neuron excitability. This screen demonstrates the power of human disease cell-based phenotypic screens for identifying clinically relevant targets for neurological disorders.
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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.