ArticleMolecular neurodegeneration2022
Differential regulation of progranulin derived granulin peptides.
Article in Molecular neurodegeneration, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 34 citations in OpenAlex.
- Hippocampal neuronal progranulin mediates estrogen‑deficiency‑induced affective vulnerability and lysosomal-autophagic dysfunction.Molecular psychiatry · 2026Article
- Tissue-specific immune and MAPK signatures in models of reduced Progranulin and Western diet.Neurobiology of disease · 2026Article
- Monospecific antibodies reveal reduction of granulins in frontotemporal dementia caused byMolecular neurodegeneration advances · 2026Article
- Progranulin deficiency in the brain: the interplay between neuronal and non-neuronal cells.Translational neurodegeneration · 2025Review
- Analysis of progranulin concentration in corneal epithelium and tears as a possible biomarker in the clinical diagnosis and progression of keratoconus.International ophthalmology · 2025Article
- Granulins rescue inflammation, lysosome dysfunction, lipofuscin, and neuropathology in a mouse model of progranulin deficiency.Cell reports · 2024Article
- Selective neuronal expression of progranulin is sufficient to provide neuroprotective and anti-inflammatory effects after traumatic brain injury.Journal of neuroinflammation · 2024Article
- Benzoxazole-derivatives enhance progranulin expression and reverse the aberrant lysosomal proteome caused by GRN haploinsufficiency.Nature communications · 2024Article
- Progranulin deficiency attenuates tubulointerstitial injury in a mouse unilateral ureteral obstruction model.Experimental animals · 2024Article
- Inhibition of cysteine protease cathepsin L increases the level and activity of lysosomal glucocerebrosidase.JCI insight · 2024Article
- Multi-modal proteomic characterization of lysosomal function and proteostasis in progranulin-deficient neurons.Molecular neurodegeneration · 2023Article
- Regulation of extracellular progranulin in medial prefrontal cortex.Neurobiology of disease · 2023Article
- Prosaposin maintains lipid homeostasis in dopamine neurons and counteracts experimental parkinsonism in rodents.Nature communications · 2023Article
- Progranulin deficiency results in sex-dependent alterations in microglia in response to demyelination.Acta neuropathologica · 2023Article
- Patients with sporadic FTLD exhibit similar increases in lysosomal proteins and storage material as patients with FTD due to GRN mutations.Acta neuropathologica communications · 2023Article
- Cab45 deficiency leads to the mistargeting of progranulin and prosaposin and aberrant lysosomal positioning.Traffic (Copenhagen, Denmark) · 2023Article
- Progranulin from different gliocytes in the nucleus accumbens exerts distinct roles in FTD- and neuroinflammation-induced depression-like behaviors.Journal of neuroinflammation · 2022Article
- Charge and redox states modulate granulin-TDP-43 coacervation toward phase separation or aggregation.Biophysical journal · 2022Article
- Regulation of lysosomal trafficking of progranulin by sortilin and prosaposin.Brain communications · 2022Article
- Microglia regulate brain progranulin levels through the endocytosis/lysosomal pathway.JCI insight · 2021Article
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundHaploinsufficiency of progranulin (PGRN) is a leading cause of frontotemporal lobar degeneration (FTLD). PGRN is comprised of 7.5 granulin repeats and is processed into individual granulin peptides in the lysosome. However, very little is known about the levels and regulations of individual granulin peptides due to the lack of specific antibodies.
resultsHere we report the generation and characterization of antibodies specific to each granulin peptide. We found that the levels of granulins C, E and F are regulated differently compared to granulins A and B in various tissues. The levels of PGRN and granulin peptides vary in different brain regions and the ratio between granulins and PGRN is highest in the cortical region in the adult male mouse brain. Granulin-A is localized in the lysosome in both neurons and microglia and its levels in microglia increase under pathological conditions. Interestingly, the levels of granulin A in microglia change correspondingly with PGRN in response to stroke but not demyelination. Furthermore, deficiency of lysosomal proteases and the PGRN binding partner prosaposin leads to alterations in the ratios between individual granulin peptides. Granulins B, C and E are heavily glycosylated and the glycosylation patterns can be regulated.
conclusionOur results support that the levels of individual granulin peptides are differentially regulated under physiological and pathological conditions and provide novel insights into how granulin peptides function in the lysosome.
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