ArticleNature communications2022
Norepinephrine transporter defects lead to sympathetic hyperactivity in Familial Dysautonomia models.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Pooled it
- The Role of the Nervous System in Lung Disease.Current neurology and neuroscience reports · 2026Review
- Adrenomedullary Organoids Derived from Neural Crest and Schwann Cell Precursors.Research square · 2026Article
- A reproducible and physiologically relevant human iPSC-derived platform for in vitro modeling of the neurocardiac junction.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Peripheral neuron phenotypes of familial dysautonomia are rescued by AAV-mediated gene therapy.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2026Article
- Multimodal, device-based therapeutic targeting of the cardiovascular autonomic nervous system.Nature reviews. Cardiology · 2026Review
- Ultrasound-activated dual-targeted liposomes for visualized precise neuromodulation against myocardial ischemia-reperfusion injury.Materials today. Bio · 2026Article
- Sympathetic-like-integrated engineered heart tissue models AGEs-induced adverse remodeling.Cardiovascular diabetology · 2026Article
- CRISPR/Cas9-mediatedFrontiers in physiology · 2026Article
- Peripheral neuron phenotypes of familial dysautonomia are rescued by AAV-mediated gene therapy.Research square · 2025Article
- Modelling neurocardiac physiology and diseases using human pluripotent stem cells: current progress and future prospects.The Journal of physiology · 2025Review
- Molecular and cellular neurocardiology in heart disease.The Journal of physiology · 2025Review
- Engineered CRISPR-Base Editors as a Permanent Treatment for Familial Dysautonomia.bioRxiv : the preprint server for biology · 2024Article
- Genipin rescues developmental and degenerative defects in familial dysautonomia models and accelerates axon regeneration.Science translational medicine · 2024Article
- Article
- Role of the sympathetic nervous system in cancer-associated cachexia and tumor progression in tumor-bearing BALB/c mice.BMC neuroscience · 2024Article
- Advances and challenges in modeling inherited peripheral neuropathies using iPSCs.Experimental & molecular medicine · 2024Review
- Parasympathetic neurons derived from human pluripotent stem cells model human diseases and development.Cell stem cell · 2024Article
- A modular platform to generate functional sympathetic neuron-innervated heart assembloids.Research square · 2024Article
- Transcriptome analysis in a humanized mouse model of familial dysautonomia reveals tissue-specific gene expression disruption in the peripheral nervous system.Scientific reports · 2024Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Familial dysautonomia (FD), a rare neurodevelopmental and neurodegenerative disorder affects the sympathetic and sensory nervous system. Although almost all patients harbor a mutation in ELP1, it remains unresolved exactly how function of sympathetic neurons (symNs) is affected; knowledge critical for understanding debilitating disease hallmarks, including cardiovascular instability or dysautonomic crises, that result from dysregulated sympathetic activity. Here, we employ the human pluripotent stem cell (hPSC) system to understand symN disease mechanisms and test candidate drugs. FD symNs are intrinsically hyperactive in vitro, in cardiomyocyte co-cultures, and in animal models. We report reduced norepinephrine transporter expression, decreased intracellular norepinephrine (NE), decreased NE re-uptake, and excessive extracellular NE in FD symNs. SymN hyperactivity is not a direct ELP1 mutation result, but may connect to NET via RAB proteins. We found that candidate drugs lowered hyperactivity independent of ELP1 modulation. Our findings may have implications for other symN disorders and may allow future drug testing and discovery.
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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.