ArticleMolecular psychiatry2015
Modeling non-syndromic autism and the impact of TRPC6 disruption in human neurons.
Article in Molecular psychiatry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 139 papers, 1 of them a synthesis that pooled it.
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Who cites it
139 citing papers in PubMed, 1 synthesis or guideline pooled it, 247 citations in OpenAlex.
- Mental health dished up-the use of iPSC models in neuropsychiatric research.Journal of neural transmission (Vienna, Austria : 1996) · 2020Pooled it
- Review
- Contribution of Copy Number Variants and Cumulative Genetic Load to Autism Spectrum Disorders: Integrative Insights from Chromosomal Microarray Analysis.International journal of molecular sciences · 2026Article
- "SHANK3 deficiency alters early progenitor dynamics and reveals shared pathways with neurodegeneration".Molecular psychiatry · 2026Article
- Neuroinflammatory mechanisms and pharmacological advances in autism spectrum disorder: from inflammatory pathways to targeted interventions.Frontiers in immunology · 2026Review
- A scoping review of stem cell models of leukodystrophies: advances in understanding pathophysiological mechanisms.NPJ genomic medicine · 2025Article
- Structure-Guided Discovery of Benzoic-Acid-Based TRPC6 Ligands: An Integrated Docking, MD, and MM-GBSA SAR Study: Potential Therapeutic Molecules for Autism Spectrum Disorder.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Analysis of neuronal activity impairment in iPSC-derived neurons from idiopathic autism patients.iScience · 2025Article
- Impact of intermittent lead exposure on hominid brain evolution.Science advances · 2025Article
- Congenital Hypothyroidism Dysregulates TRPC6 to Mediate Abnormal Dendritic Spine Growth of Hippocampal Neurons.CNS neuroscience & therapeutics · 2025Article
- TRPC4 regulates limbic behavior and neuronal development by stabilizing dendrite branches through actomyosin-driven integrin activation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Soluble β-Amyloid Oligomers Selectively Upregulate TRPC3 in Excitatory Neurons via Calcineurin-Coupled NFAT.Cells · 2025Article
- Requirements for the neurodevelopmental disorder-associated gene ZNF292 in human cortical interneuron development and function.Cell reports · 2025Article
- Review
- Model systems for emulating human tissue and physiology in psychiatric research.Frontiers in neuroscience · 2025Review
- TRP channels in epileptogenesis: calcium dysregulation mechanisms and pharmacological targeting strategies.Frontiers in molecular neuroscience · 2025Review
- Loss of GTF2I promotes neuronal apoptosis and synaptic reduction in human cellular models of neurodevelopment.Cell reports · 2024Article
- Article
- TRPC4 deletion elicits behavioral defects in sociability by dysregulating expression of microRNA-138-2.iScience · 2024Article
- Advances in the Treatment of Autism Spectrum Disorder: Current and Promising Strategies.Current medicinal chemistry · 2024Review
79 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
25 authors at 9 institutions in 3 countries.
Funding
Abstract
An increasing number of genetic variants have been implicated in autism spectrum disorders (ASDs), and the functional study of such variants will be critical for the elucidation of autism pathophysiology. Here, we report a de novo balanced translocation disruption of TRPC6, a cation channel, in a non-syndromic autistic individual. Using multiple models, such as dental pulp cells, induced pluripotent stem cell (iPSC)-derived neuronal cells and mouse models, we demonstrate that TRPC6 reduction or haploinsufficiency leads to altered neuronal development, morphology and function. The observed neuronal phenotypes could then be rescued by TRPC6 complementation and by treatment with insulin-like growth factor-1 or hyperforin, a TRPC6-specific agonist, suggesting that ASD individuals with alterations in this pathway may benefit from these drugs. We also demonstrate that methyl CpG binding protein-2 (MeCP2) levels affect TRPC6 expression. Mutations in MeCP2 cause Rett syndrome, revealing common pathways among ASDs. Genetic sequencing of TRPC6 in 1041 ASD individuals and 2872 controls revealed significantly more nonsynonymous mutations in the ASD population, and identified loss-of-function mutations with incomplete penetrance in two patients. Taken together, these findings suggest that TRPC6 is a novel predisposing gene for ASD that may act in a multiple-hit model. This is the first study to use iPSC-derived human neurons to model non-syndromic ASD and illustrate the potential of modeling genetically complex sporadic diseases using such cells.
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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.