ArticleNature communications2015
RCAN1 links impaired neurotrophin trafficking to aberrant development of the sympathetic nervous system in Down syndrome.
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 64 citations in OpenAlex.
- Perinatal liver sympathetic innervation governs body size.Communications biology · 2026Article
- Calcineurin inhibition may prevent Alzheimer disease in people with Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Hormonal Imbalance as a Prognostic Factor of Physical Development of Children with Intellectual Disability.Children (Basel, Switzerland) · 2024Article
- SARS-CoV-2 Infection Causes Heightened Disease Severity and Mortality in a Mouse Model of Down Syndrome.Biomedicines · 2024Article
- Transcytosis-mediated anterograde transport of TrkA receptors is necessary for sympathetic neuron development and function.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Clinical characteristics and comorbidities of COVID-19 in unvaccinated patients with Down syndrome: first year report in Brazil.Human genetics · 2022Article
- Neurobiology, Stem Cell Biology, and Immunology: An Emerging Triad for Understanding Tissue Homeostasis and Repair.Annual review of cell and developmental biology · 2022Review
- Min pig skeletal muscle response to cold stress.PloS one · 2022Review
- Specific Susceptibility to COVID-19 in Adults with Down Syndrome.Neuromolecular medicine · 2021Article
- The sympathetic nervous system in development and disease.Nature reviews. Neuroscience · 2021Review
- The transcriptome profile of human trisomy 21 blood cells.Human genomics · 2021Article
- Targeting increased levels of APP in Down syndrome: Posiphen-mediated reductions in APP and its products reverse endosomal phenotypes in the Ts65Dn mouse model.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2021Article
- NGF Signaling in Endosomes.Advances in experimental medicine and biology · 2021Article
- Down Syndrome Critical Region 1 Reduces Oxidative Stress-Induced Retinal Ganglion Cells Apoptosis via CREB-Bcl-2 Pathway.Investigative ophthalmology & visual science · 2020Article
- Regulator of Calcineurin (RCAN): Beyond Down Syndrome Critical Region.Molecules and cells · 2020Review
- Adults with Down syndrome challenge another paradigm: When aging no longer entails arterial hypertension.Journal of clinical hypertension (Greenwich, Conn.) · 2020Review
- Prenylation of Axonally Translated Rac1 Controls NGF-Dependent Axon Growth.Developmental cell · 2020Article
- The Adult Ts65Dn Mouse Model of Down Syndrome Shows Altered Swallow Function.Frontiers in neuroscience · 2019Article
- Human Models Are Needed for Studying Human Neurodevelopmental Disorders.American journal of human genetics · 2018Review
- Mechanisms of neurotrophin trafficking via Trk receptors.Molecular and cellular neurosciences · 2018Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Down syndrome is the most common chromosomal disorder affecting the nervous system in humans. To date, investigations of neural anomalies in Down syndrome have focused on the central nervous system, although dysfunction of the peripheral nervous system is a common manifestation. The molecular and cellular bases underlying peripheral abnormalities have remained undefined. Here, we report the developmental loss of sympathetic innervation in human Down syndrome organs and in a mouse model. We show that excess regulator of calcineurin 1 (RCAN1), an endogenous inhibitor of the calcineurin phosphatase that is triplicated in Down syndrome, impairs neurotrophic support of sympathetic neurons by inhibiting endocytosis of the nerve growth factor (NGF) receptor, TrkA. Genetically correcting RCAN1 levels in Down syndrome mice markedly improves NGF-dependent receptor trafficking, neuronal survival and innervation. These results uncover a critical link between calcineurin signalling, impaired neurotrophin trafficking and neurodevelopmental deficits in the peripheral nervous system in Down syndrome.
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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.