ArticleEMBO molecular medicine2020
Huntingtin phosphorylation governs BDNF homeostasis and improves the phenotype of Mecp2 knockout mice.
Article in EMBO molecular medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 29 citations in OpenAlex.
- KIF1A-associated neurological disorders: therapeutic opportunities and challenges.European journal of human genetics : EJHG · 2026Review
- Huntingtin polyglutamine expansions misdirect axonal transport by perturbing motor and adaptor recruitment.iScience · 2026Article
- Leptin antagonism improves Rett syndrome phenotype in symptomatic Mecp2-deficient mice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Post-Translational Modifications of Huntingtin: Mechanistic Insights and Therapeutic Opportunities in Huntington's Disease.International journal of molecular sciences · 2025Review
- Unveiling Molecular Dynamics of MeCp2, CDKL5 and BDNF in the Hippocampus of Individuals With Intractable Mesial Temporal Lobe Epilepsy.Journal of cellular and molecular medicine · 2025Article
- Roscovitine, a CDK Inhibitor, Reduced Neuronal Toxicity of mHTT by Targeting HTT Phosphorylation at S1181 and S1201 In Vitro.International journal of molecular sciences · 2024Article
- Presynaptic perspective: Axonal transport defects in neurodevelopmental disorders.The Journal of cell biology · 2024Review
- Article
- Microfluidic Bi-Layer Platform to Study Functional Interaction between Co-Cultured Neural Networks with Unidirectional Synaptic Connectivity.Micromachines · 2023Article
- Huntingtin S421 phosphorylation increases kinesin and dynein engagement on early endosomes and lysosomes.Biophysical journal · 2023Article
- A cellular atlas of calcineurin signaling.Biochimica et biophysica acta. Molecular cell research · 2023Review
- Molecular Pathophysiological Mechanisms in Huntington's Disease.Biomedicines · 2022Review
- Loss of neurodevelopmental-associated miR-592 impairs neurogenesis and causes social interaction deficits.Cell death & disease · 2022Article
- Regulation of sensorimotor gating via Disc1/Huntingtin-mediated Bdnf transport in the cortico-striatal circuit.Molecular psychiatry · 2022Article
- Calcineurin and huntingtin form a calcium-sensing machinery that directs neurotrophic signals to the nucleus.Science advances · 2022Article
- Transcriptional Regulation ofBiomolecules · 2021Article
- Transcriptomic and Epigenomic Landscape in Rett Syndrome.Biomolecules · 2021Review
- Analysis of Astroglial Secretomic Profile in the Mecp2-Deficient Male Mouse Model of Rett Syndrome.International journal of molecular sciences · 2021Article
- Recreating mouse cortico-hippocampal neuronal circuit in microfluidic devices to study BDNF axonal transport upon glucocorticoid treatment.STAR protocols · 2021Article
- The Pathophysiology of Rett Syndrome With a Focus on Breathing Dysfunctions.Physiology (Bethesda, Md.) · 2020Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Mutations in the X-linked MECP2 gene are responsible for Rett syndrome (RTT), a severe neurological disorder for which there is no treatment. Several studies have linked the loss of MeCP2 function to alterations of brain-derived neurotrophic factor (BDNF) levels, but non-specific overexpression of BDNF only partially improves the phenotype of Mecp2-deficient mice. We and others have previously shown that huntingtin (HTT) scaffolds molecular motor complexes, transports BDNF-containing vesicles, and is under-expressed in Mecp2 knockout brains. Here, we demonstrate that promoting HTT phosphorylation at Ser421, either by a phospho-mimetic mutation or inhibition of the phosphatase calcineurin, restores endogenous BDNF axonal transport in vitro in the corticostriatal pathway, increases striatal BDNF availability and synaptic connectivity in vivo, and improves the phenotype and the survival of Mecp2 knockout mice-even though treatments were initiated only after the mice had already developed symptoms. Stimulation of endogenous cellular pathways may thus be a promising approach for the treatment of RTT patients.
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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.