ArticleMolecular neurodegeneration2016
Progranulin promotes peripheral nerve regeneration and reinnervation: role of notch signaling.
Article in Molecular neurodegeneration, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 75 citations in OpenAlex.
- Synergistic cooperation between progranulin and Jak2/Stat3 signaling determines definitive myeloid cell fate.Cell reports · 2026Article
- Molecular phenotypes stratify small cell lung cancer for targeted therapy and immunotherapy.British journal of cancer · 2026Article
- Article
- Progranulin deficiency in the brain activates an insulin signaling pathway that may promote neurodegeneration.iScience · 2026Article
- Selective neuronal restoration of progranulin does not prevent the frontotemporal dementia like-phenotype of progranulin knockout mice.Journal of neuroinflammation · 2026Article
- Article
- Delivering Progranulin to Astrocytic Lysosomes Promotes Growth of Co-Cultured Neurons.Journal of neurochemistry · 2025Article
- Brain region specific regulation of anandamide (down) and sphingosine-1-phosphate (up) in association with anxiety (AEA) and resilience (S1P) in a mouse model of chronic unpredictable mild stress.Pflugers Archiv : European journal of physiology · 2024Article
- Selective neuronal expression of progranulin is sufficient to provide neuroprotective and anti-inflammatory effects after traumatic brain injury.Journal of neuroinflammation · 2024Article
- Progranulin Facilitates Corneal Repair Through Dual Mechanisms of Inflammation Suppression and Regeneration Promotion.Inflammation · 2024Article
- Tear Fluid Progranulin as a Noninvasive Biomarker for the Monitoring of Corneal Innervation Changes in Patients With Type 2 Diabetes Mellitus.Translational vision science & technology · 2024Article
- Progranulinopathy: A diverse realm of disorders linked to progranulin imbalances.Cytokine & growth factor reviews · 2024Review
- Targeting Progranulin as an Immuno-Neurology Therapeutic Approach.International journal of molecular sciences · 2023Review
- Regulation of extracellular progranulin in medial prefrontal cortex.Neurobiology of disease · 2023Article
- IRE1α protects against osteoarthritis by regulating progranulin-dependent XBP1 splicing and collagen homeostasis.Experimental & molecular medicine · 2023Article
- Progranulin and EGFR modulate receptor-like tyrosine kinase sorting and stability in mesothelioma cells.American journal of physiology. Cell physiology · 2023Article
- Progranulin Oncogenic Network in Solid Tumors.Cancers · 2023Review
- Review
- TDP-43 condensates and lipid droplets regulate the reactivity of microglia and regeneration after traumatic brain injury.Nature neuroscience · 2022Article
- Progranulin improves neural development via the PI3K/Akt/GSK-3β pathway in the cerebellum of a VPA-induced rat model of ASD.Translational psychiatry · 2022Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPeripheral nerve injury is a frequent cause of lasting motor deficits and chronic pain. Although peripheral nerves are capable of regrowth they often fail to re-innervate target tissues.
resultsUsing newly generated transgenic mice with inducible neuronal progranulin overexpression we show that progranulin accelerates axonal regrowth, restoration of neuromuscular synapses and recovery of sensory and motor functions after injury of the sciatic nerve. Oppositely, progranulin deficient mice have long-lasting deficits in motor function tests after nerve injury due to enhanced losses of motor neurons and stronger microglia activation in the ventral horn of the spinal cord. Deep proteome and gene ontology (GO) enrichment analysis revealed that the proteins upregulated in progranulin overexpressing mice were involved in 'regulation of transcription' and 'response to insulin' (GO terms). Transcription factor prediction pointed to activation of Notch signaling and indeed, co-immunoprecipitation studies revealed that progranulin bound to the extracellular domain of Notch receptors, and this was functionally associated with higher expression of Notch target genes in the dorsal root ganglia of transgenic mice with neuronal progranulin overexpression. Functionally, these transgenic mice recovered normal gait and running, which was not achieved by controls and was stronger impaired in progranulin deficient mice.
conclusionWe infer that progranulin activates Notch signaling pathways, enhancing thereby the regenerative capacity of partially injured neurons, which leads to improved motor function recovery.
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Registered trials
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