ArticleNature aging2024
Longitudinal modeling of human neuronal aging reveals the contribution of the RCAN1-TFEB pathway to Huntington's disease neurodegeneration.
Article in Nature aging, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 18 citations in OpenAlex.
- Identification of Age-Associated Upstream Regulators to Promote Neuronal Resilience in HD Patient-Derived Neurons.Neuroscience bulletin · 2026Article
- Apelin-13 prevents GATA4-mediated neuronal senescence by restoring autophagy through mTORC1 inhibition.Cell death & disease · 2026Article
- Cross-species functional analysis of aResearch square · 2026Article
- DYRK1A and Parkinson's disease, facts and hypotheses.Neurobiology of disease · 2026Review
- Insights into the therapeutic strategies for aging and aging-associated diseases.Signal transduction and targeted therapy · 2026Review
- A pathogenic Tau mutation drives autophagy-lysosome dysfunction that limits Tau degradation in a model of frontotemporal dementia.Nature communications · 2026Article
- Impairment of lysosomal quality control in Huntington disease.Cell death & disease · 2025Article
- Sequelae and reversal of age-dependent alterations in mitochondrial dynamics via autophagy enhancement in reprogrammed human neurons.bioRxiv : the preprint server for biology · 2025Article
- Expansion of lysosomal capacity in early adult neurons driven by TFEB/HLH-30 protects dendrite maintenance during aging in Caenorhabditis elegans.PLoS biology · 2025Article
- Monitoring Autophagy in Human Aging: Key Cell Models and Insights.Frontiers in bioscience (Landmark edition) · 2025Review
- Are oligodendrocytes bystanders or drivers of Parkinson's disease pathology?PLoS biology · 2025Article
- Short Peptides Protect Fibroblast-Derived Induced Neurons from Age-Related Changes.International journal of molecular sciences · 2024Article
- A metabolomic profile of biological aging in 250,341 individuals from the UK Biobank.Nature communications · 2024Article
- Age- and disease-related autophagy impairment in Huntington disease: New insights from direct neuronal reprogramming.Aging cell · 2024Review
- Role of TFEB in Huntington's Disease.Biology · 2024Review
- Cellular reprogramming as a tool to model human aging in a dish.Nature communications · 2024Review
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12 authors at 3 institutions in 1 country.
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Abstract
Aging is a common risk factor in neurodegenerative disorders. Investigating neuronal aging in an isogenic background stands to facilitate analysis of the interplay between neuronal aging and neurodegeneration. Here we perform direct neuronal reprogramming of longitudinally collected human fibroblasts to reveal genetic pathways altered at different ages. Comparative transcriptome analysis of longitudinally aged striatal medium spiny neurons (MSNs) in Huntington's disease identified pathways involving RCAN1, a negative regulator of calcineurin. Notably, RCAN1 protein increased with age in reprogrammed MSNs as well as in human postmortem striatum and RCAN1 knockdown rescued patient-derived MSNs of Huntington's disease from degeneration. RCAN1 knockdown enhanced chromatin accessibility of genes involved in longevity and autophagy, mediated through enhanced calcineurin activity, leading to TFEB's nuclear localization by dephosphorylation. Furthermore, G2-115, an analog of glibenclamide with autophagy-enhancing activities, reduced the RCAN1-calcineurin interaction, phenocopying the effect of RCAN1 knockdown. Our results demonstrate that targeting RCAN1 genetically or pharmacologically can increase neuronal resilience in Huntington's disease.
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