ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2024
ZCCHC17 Modulates Neuronal RNA Splicing and Supports Cognitive Resilience in Alzheimer's Disease.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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9 citing papers in PubMed, 11 citations in OpenAlex.
- Genetic Heterogeneity of Autism Spectrum Disorder: Identification of Five Novel Mutations (RIMS2, FOXG1, AUTS2, ZCCHC17, and SPTBN5) in Iranian Families via Whole-Exome and Whole-Genome Sequencing.Biochemical genetics · 2026Article
- ZCCHC17: a target for synaptic dysfunction and neuronal excitability in Alzheimer's disease.Frontiers in aging neuroscience · 2026Review
- High throughput identification of genetic regulators of microglial inflammatory processes in Alzheimer's disease.Journal of neuroinflammation · 2025Article
- Iso-seq and RNA-seq data from ML-2 acute myeloid leukemia cells overexpressing the ZCCHC10 gene.Data in brief · 2025Article
- An analysis of RNA quality metrics in human brain tissue.Journal of neuropathology and experimental neurology · 2025Article
- The transcriptional and cellular landscape of cognitive resilience to Alzheimer's disease.Frontiers in molecular neuroscience · 2025Review
- Generating iAstrocytes From Human Induced Pluripotent Stem Cells by Combining Low-Density Passaging of Neural Progenitor Cells and Transcription Factor NFIA Transdifferentiation.Current protocols · 2024Article
- Predicting Alzheimer's Cognitive Resilience Score: A Comparative Study of Machine Learning Models Using RNA-seq Data.bioRxiv : the preprint server for biology · 2024Article
- ZCCHC17 knockdown phenocopies Alzheimer's disease-related loss of synaptic proteins and hyperexcitability.Journal of neuropathology and experimental neurology · 2024Article
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23 authors at 9 institutions in 1 country.
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Abstract
ZCCHC17 is a putative master regulator of synaptic gene dysfunction in Alzheimer's disease (AD), and ZCCHC17 protein declines early in AD brain tissue, before significant gliosis or neuronal loss. Here, we investigate the function of ZCCHC17 and its role in AD pathogenesis using data from human autopsy tissue (consisting of males and females) and female human cell lines. Co-immunoprecipitation (co-IP) of ZCCHC17 followed by mass spectrometry analysis in human iPSC-derived neurons reveals that ZCCHC17's binding partners are enriched for RNA-splicing proteins. ZCCHC17 knockdown results in widespread RNA-splicing changes that significantly overlap with splicing changes found in AD brain tissue, with synaptic genes commonly affected. ZCCHC17 expression correlates with cognitive resilience in AD patients, and we uncover an APOE4-dependent negative correlation of ZCCHC17 expression with tangle burden. Furthermore, a majority of ZCCHC17 interactors also co-IP with known tau interactors, and we find a significant overlap between alternatively spliced genes in ZCCHC17 knockdown and tau overexpression neurons. These results demonstrate ZCCHC17's role in neuronal RNA processing and its interaction with pathology and cognitive resilience in AD, and suggest that the maintenance of ZCCHC17 function may be a therapeutic strategy for preserving cognitive function in the setting of AD pathology.
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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.