ArticleNature communications2024
Reduced progranulin increases tau and α-synuclein inclusions and alters mouse tauopathy phenotypes via glucocerebrosidase.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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.
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Who cites it
21 citing papers in PubMed, 22 citations in OpenAlex.
- In vivo detection of pathologic α- synuclein and TDP-43 in the skin and olfactory mucosa of a patient with Parkinson's disease-like phenotype carrying the p.Thr272Serfs*10 GRN mutation.Molecular neurodegeneration · 2026Article
- CXCL10 contributes to female-specific pathological progression in tauopathy model mice.Journal of neuroinflammation · 2026Article
- Proteomic comparison of hippocampal neurofibrillary tangles in PART, intermediate Alzheimer's disease and advanced Alzheimer's disease.Acta neuropathologica · 2026Article
- Protein kinase CK2α' as a dual modulator of neuroimmune signaling and synaptic dysfunction in tauopathy.Translational neurodegeneration · 2026Article
- Endosomes as central hubs of interorganellar communication and cellular homeostasis.Protein & cell · 2026Review
- Targeting the PGRN-BMP Lysosomal Axis With NPs@PGRN Reverses Immunometabolic Dysfunction in Chronic Septic Arthritis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Pathogenic or Likely Pathogenic GRN Variants Are Found in 0.1% of Parkinson's Disease Patients.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Proteomic remodelling of the neurofibrillary tangle from "PART" to advanced Alzheimer's disease.Research square · 2026Article
- Nano-PROTACs for precision medicine: engineering strategies for enhanced targeting and potency.Journal of nanobiotechnology · 2026Review
- Article
- Protein kinase CK2α' as a dual modulator of immune signaling and synaptic dysfunction in Tauopathy.bioRxiv : the preprint server for biology · 2025Article
- Potential of phytochemicals in the treatment of Alzheimer disease by modulating lysosomal dysfunction: a systematic review.Chinese medicine · 2025Review
- The role of endolysosomal progranulin and TMEM106B in neurodegenerative diseases.Molecular neurodegeneration · 2025Review
- From Amyloid to Synaptic Dysfunction: Biomarker-Driven Insights into Alzheimer's Disease.Current issues in molecular biology · 2025Review
- Progranulin Mutation Manifesting as Parkinson Disease: A Case Series from the PADUA-CESNE Cohort.Movement disorders clinical practice · 2025Article
- Revisiting the therapeutic landscape of tauopathies: assessing the current pipeline and clinical trials.Alzheimer's research & therapy · 2025Review
- Broken Balance: Emerging Cross-Talk Between Proteostasis and Lipostasis in Neurodegenerative Diseases.Cells · 2025Review
- PGRN as an emerging regulator of lipid metabolism in neurodegenerative diseases.Communications biology · 2025Review
- Differences in the soluble and insoluble proteome between primary tauopathies.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Progranulin deficiency in the brain: the interplay between neuronal and non-neuronal cells.Translational neurodegeneration · 2025Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
Comorbid proteinopathies are observed in many neurodegenerative disorders including Alzheimer's disease (AD), increase with age, and influence clinical outcomes, yet the mechanisms remain ill-defined. Here, we show that reduction of progranulin (PGRN), a lysosomal protein associated with TDP-43 proteinopathy, also increases tau inclusions, causes concomitant accumulation of α-synuclein and worsens mortality and disinhibited behaviors in tauopathy mice. The increased inclusions paradoxically protect against spatial memory deficit and hippocampal neurodegeneration. PGRN reduction in male tauopathy attenuates activity of β-glucocerebrosidase (GCase), a protein previously associated with synucleinopathy, while increasing glucosylceramide (GlcCer)-positive tau inclusions. In neuronal culture, GCase inhibition enhances tau aggregation induced by AD-tau. Furthermore, purified GlcCer directly promotes tau aggregation in vitro. Neurofibrillary tangles in human tauopathies are also GlcCer-immunoreactive. Thus, in addition to TDP-43, PGRN regulates tau- and synucleinopathies via GCase and GlcCer. A lysosomal PGRN-GCase pathway may be a common therapeutic target for age-related comorbid proteinopathies.
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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.