ArticleNature communications2022
Deficiency of the frontotemporal dementia gene GRN results in gangliosidosis.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 95 citations in OpenAlex.
- Research trends and hotspots for frontotemporal dementia from 2000 to 2022: a bibliometric analysis.Frontiers in neurology · 2024Pooled it
- Progranulin AAV gene therapy for frontotemporal dementia: translational studies and phase 1/2 trial interim results.Nature medicine · 2024Trial
- Batten disease protein CLN8 enables a non-canonical phospholipid synthesis pathway.Nature cell biology · 2026Article
- Human TDP-43 expression worsens FTD-related phenotypes in progranulin-insufficient mice.Neurobiology of disease · 2026Article
- Shared lipidome and proteome signatures of frontotemporal lobar degeneration and Alzheimer's disease.Research square · 2026Article
- TGF-β signaling promotes astroglial activation and TDP-43 proteinopathy in organoid models of frontotemporal lobar degeneration.The Journal of clinical investigation · 2026Article
- A human lysosomal storage disorder toolkit for decoding proteome landscapes in cortical-like and dopaminergic-like induced neurons.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Synergistic cooperation between progranulin and Jak2/Stat3 signaling determines definitive myeloid cell fate.Cell reports · 2026Article
- Robust analytical methods for bis(monoacylglycero)phosphate profiling in health and disease.Nature protocols · 2026Review
- Integration of single-cell RNA-sequencing and machine learning identifies GRN and FCER1G as potential peroxisomal targets in influenza pathogenesis.BMC infectious diseases · 2026Article
- Article
- Translational lipidomics reveals BMP and its precursor LPG as biomarkers for CLN5 Batten disease.bioRxiv : the preprint server for biology · 2026Article
- The Phospholipid Bis(monoacylglycero)Phosphate Confers Antitumour Immunogenicity to Exosomes Secreted by Dendrogenin A, Which Activates Its Biosynthesis in Tumour Cells.Journal of extracellular vesicles · 2026Article
- Glycosphingolipids in Dementia: Insights from Mass Spectrometry and Systems Biology Approaches.Biomedicines · 2025Review
- Delivering Progranulin to Astrocytic Lysosomes Promotes Growth of Co-Cultured Neurons.Journal of neurochemistry · 2025Article
- Microglia-specific regulation of lipid metabolism in Alzheimer's disease revealed by microglial depletion in 5xFAD Mice.Nature communications · 2025Article
- Targeting Granulin Haploinsufficiency in Frontotemporal Dementia: From Genetic Mechanisms to Therapeutics.International journal of molecular sciences · 2025Review
- Ablation of progranulin augments microglial activation and accelerates prion progression.Acta neuropathologica communications · 2025Article
- Proteome Landscapes Decode Organelle Vulnerabilities in cortical and dopaminergic-like induced neurons Across Lysosomal Storage Disorders.bioRxiv : the preprint server for biology · 2025Article
- Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 4 institutions in 1 country.
Funding
Abstract
Haploinsufficiency of GRN causes frontotemporal dementia (FTD). The GRN locus produces progranulin (PGRN), which is cleaved to lysosomal granulin polypeptides. The function of lysosomal granulins and why their absence causes neurodegeneration are unclear. Here we discover that PGRN-deficient human cells and murine brains, as well as human frontal lobes from GRN-mutation FTD patients have increased levels of gangliosides, glycosphingolipids that contain sialic acid. In these cells and tissues, levels of lysosomal enzymes that catabolize gangliosides were normal, but levels of bis(monoacylglycero)phosphates (BMP), lipids required for ganglioside catabolism, were reduced with PGRN deficiency. Our findings indicate that granulins are required to maintain BMP levels to support ganglioside catabolism, and that PGRN deficiency in lysosomes leads to gangliosidosis. Lysosomal ganglioside accumulation may contribute to neuroinflammation and neurodegeneration susceptibility observed in FTD due to PGRN deficiency and other neurodegenerative diseases.
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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.