ArticleCell reports2021
Microglial lysosome dysfunction contributes to white matter pathology and TDP-43 proteinopathy in GRN-associated FTD.
Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
58 citing papers in PubMed, 81 citations in OpenAlex.
- Human TDP-43 expression worsens FTD-related phenotypes in progranulin-insufficient mice.Neurobiology of disease · 2026Article
- Proteostasis of organelles in aging and disease.The FEBS journal · 2026Review
- Youth-associated protein TIMP2 regulates microglial state and function in healthy and aged mice.Nature communications · 2026Article
- Article
- Association Between Progranulin (PGRN) Levels in Serum and Cerebrospinal Fluid with Integrated Clinical Indices in Patients with Idiopathic Normal Pressure Hydrocephalus.Journal of clinical medicine · 2026Article
- Progranulin deficiency perturbs lipid metabolism in white matter microglia.bioRxiv : the preprint server for biology · 2026Article
- Inhibition of SLC11A1-Mediated Lysosomal Iron Accumulation in Microglia Promotes Repair Following White Matter Stroke.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Regulation of microglial activation by progranulin through the NF-κB pathway in subarachnoid hemorrhage and its effect on white matter injury.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Control of microglial dynamics by the Arp2/3 complex and the autism- and schizophrenia-associated protein CYFIP1.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Phagocytosis and neuroinflammation: orchestrating central nervous system homeostasis, repair, and the resolution of inflammation.Trends in neurosciences · 2026Review
- Inducible deletion of DGAT1 and 2 from microglia exacerbates neurodegeneration and endolysosomal lipid accumulation in male PS19 mice.Cell reports · 2026Article
- Peroxisomal integrity in demyelination-associated microglia enables cellular debris clearance and myelin renewal in mice.The Journal of clinical investigation · 2026Article
- Microglial state transitions are constrained by developmental and metabolic checkpoints.Frontiers in cellular neuroscience · 2026Review
- One organelle to rule them all: enhancement of lysosomal activity as a therapeutic modality for protein misfolding neurodegenerative diseases.Frontiers in neuroscience · 2026Review
- Systemic Interleukin-4 Application Promotes Functional Recovery and Reprograms Neuroinflammatory and Molecular Responses after Spinal Cord Injury in Rats.Theranostics · 2026Article
- Multi-omic spatially resolved analysis of the neuroinflammatory response to intracortical microelectrode arrays.Biomaterials · 2026Article
- Monospecific antibodies reveal reduction of granulins in frontotemporal dementia caused byMolecular neurodegeneration advances · 2026Article
- Delivering Progranulin to Astrocytic Lysosomes Promotes Growth of Co-Cultured Neurons.Journal of neurochemistry · 2025Article
- Rutin ameliorates sevoflurane-induced neurotoxicity by inhibiting microglial synaptic phagocytosis through the complement pathway.Scientific reports · 2025Article
- Ablation of progranulin augments microglial activation and accelerates prion progression.Acta neuropathologica communications · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
Loss-of-function mutations in the progranulin gene (GRN), which encodes progranulin (PGRN), are a major cause of frontotemporal dementia (FTD). GRN-associated FTD is characterized by TDP-43 inclusions and neuroinflammation, but how PGRN loss causes disease remains elusive. We show that Grn knockout (KO) mice have increased microgliosis in white matter and an accumulation of myelin debris in microglial lysosomes in the same regions. Accumulation of myelin debris is also observed in white matter of patients with GRN-associated FTD. In addition, our findings also suggest that PGRN insufficiency in microglia leads to impaired lysosomal-mediated clearance of myelin debris. Finally, Grn KO mice that are deficient in cathepsin D (Ctsd), a key lysosomal enzyme, have augmented myelin debris and increased neuronal TDP-43 pathology. Together, our data strongly imply that PGRN loss affects microglial activation and lysosomal function, resulting in the accumulation of myelin debris and contributing to TDP-43 pathology.
Indexed as
Identifiers
What OpenQuestion holds
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.