ArticleNeuron2011
Functional genomic analyses identify pathways dysregulated by progranulin deficiency, implicating Wnt signaling.
Article in Neuron, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 130 citations in OpenAlex.
- Insights from cerebellar transcriptomic analysis into the pathogenesis of ataxia.JAMA neurology · 2014Trial
- Progranulin haploinsufficiency remodels the cerebral microvasculature and neurovascular unit.bioRxiv : the preprint server for biology · 2026Article
- Progranulin deficiency in the brain: the interplay between neuronal and non-neuronal cells.Translational neurodegeneration · 2025Review
- Fluid biomarkers in familial frontotemporal dementia: progress and prospects.Frontiers in neurology · 2025Review
- Mutant GGGGCC RNA prevents YY1 from binding to Fuzzy promoter which stimulates Wnt/β-catenin pathway in C9ALS/FTD.Nature communications · 2023Article
- Granulin loss of function in human mature brain organoids implicates astrocytes in TDP-43 pathology.Stem cell reports · 2023Article
- Progranulin Oncogenic Network in Solid Tumors.Cancers · 2023Review
- Progranulin (PGRN) as a regulator of inflammation and a critical factor in the immunopathogenesis of cardiovascular diseases.Journal of inflammation (London, England) · 2023Review
- Conserved gene signatures shared amongFrontiers in molecular biosciences · 2023Article
- Progranulin is an FMRP target that influences macroorchidism but not behaviour in a mouse model of Fragile X Syndrome.Current research in neurobiology · 2023Article
- Targeting RPL23 restores chemosensitivity of cisplatin-resistant ovarian carcinoma by inhibiting EMT.Cytotechnology · 2022Article
- CILP, a Putative Gene Associated With Immune Infiltration in Breast Cancer Brain Metastases.Frontiers in genetics · 2022Article
- Parkin beyond Parkinson's Disease-A Functional Meaning of Parkin Downregulation in TDP-43 Proteinopathies.Cells · 2021Review
- Microglia regulate brain progranulin levels through the endocytosis/lysosomal pathway.JCI insight · 2021Article
- Brain-trait-associated variants impact cell-type-specific gene regulation during neurogenesis.American journal of human genetics · 2021Article
- Tenascin-C promotes epithelial-to-mesenchymal transition and the mTOR signaling pathway in nasopharyngeal carcinoma.Oncology letters · 2021Article
- Immune signature-based hepatocellular carcinoma subtypes may provide novel insights into therapy and prognosis predictions.Cancer cell international · 2021Article
- Transcriptomic networks implicate neuronal energetic abnormalities in three mouse models harboring autism and schizophrenia-associated mutations.Molecular psychiatry · 2021Article
- Differential Regulation of Wnt Signaling Components During Hippocampal Reorganization After Entorhinal Cortex Lesion.Cellular and molecular neurobiology · 2021Article
- Transcriptomic and Network Meta-Analysis of Frontotemporal Dementias.Frontiers in molecular neuroscience · 2021Article
28 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Progranulin (GRN) mutations cause frontotemporal dementia (FTD), but GRN's function in the CNS remains largely unknown. To identify the pathways downstream of GRN, we used weighted gene coexpression network analysis (WGCNA) to develop a systems-level view of transcriptional alterations in a human neural progenitor model of GRN-deficiency. This highlighted key pathways such as apoptosis and ubiquitination in GRN deficient human neurons, while revealing an unexpected major role for the Wnt signaling pathway, which was confirmed by analysis of gene expression data from postmortem FTD brain. Furthermore, we observed that the Wnt receptor Fzd2 was one of only a few genes upregulated at 6 weeks in a GRN knockout mouse, and that FZD2 reduction caused increased apoptosis, while its upregulation promoted neuronal survival in vitro. Together, these in vitro and in vivo data point to an adaptive role for altered Wnt signaling in GRN deficiency-mediated FTD, representing a potential therapeutic target.
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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.