ArticleJournal of molecular biology2019
Progranulin Stimulates the In Vitro Maturation of Pro-Cathepsin D at Acidic pH.
Article in Journal of molecular biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 89 citations in OpenAlex.
- Progranulin AAV gene therapy for frontotemporal dementia: translational studies and phase 1/2 trial interim results.Nature medicine · 2024Trial
- Lysosomal dysfunction in neurodegenerative disease.Nature reviews. Neurology · 2026Review
- Hippocampal neuronal progranulin mediates estrogen‑deficiency‑induced affective vulnerability and lysosomal-autophagic dysfunction.Molecular psychiatry · 2026Article
- Progranulin promotes glioma progression via interaction with cathepsin D and serves as a diagnostic and prognostic biomarker.Discover oncology · 2026Article
- Prosaposin Is Cleaved Into Saposins by Multiple Cathepsins in a Progranulin-Regulated Fashion.Journal of neurochemistry · 2026Article
- Lysosomal protease-mediated APP degradation is pH-dependent, mutation-sensitive, and facilitates tau proteolysis.Molecular neurodegeneration advances · 2026Article
- Reduction of sphingomyelinase activity associated with progranulin deficiency and frontotemporal dementia.Neurobiology of disease · 2025Article
- The role of endolysosomal progranulin and TMEM106B in neurodegenerative diseases.Molecular neurodegeneration · 2025Review
- TFEB overexpression alleviates autophagy-lysosomal deficits caused by progranulin insufficiency.Scientific reports · 2025Article
- Progranulin deficiency in the brain: the interplay between neuronal and non-neuronal cells.Translational neurodegeneration · 2025Review
- Intrinsic link between PGRN and Gba1 D409V mutation dosage in potentiating Gaucher disease.Human molecular genetics · 2024Article
- Sortilin is associated with progranulin deficiency and autism-like behaviors in valproic acid-induced autism rats.CNS neuroscience & therapeutics · 2024Article
- Alternative proteoforms and proteoform-dependent assemblies in humans and plants.Molecular systems biology · 2024Article
- Benzoxazole-derivatives enhance progranulin expression and reverse the aberrant lysosomal proteome caused by GRN haploinsufficiency.Nature communications · 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
- The progranulin cleavage product granulin 3 exerts a dominant negative effect on animal fitness.Human molecular genetics · 2024Article
- Progranulin and GPNMB: interactions in endo-lysosome function and inflammation in neurodegenerative disease.Journal of neuroinflammation · 2023Review
- AAV-iScience · 2023Article
- Latozinemab, a novel progranulin-elevating therapy for frontotemporal dementia.Journal of translational medicine · 2023Article
- Identification of Fangjihuangqi Decoction as a late-stage autophagy inhibitor with an adjuvant anti-tumor effect against non-small cell lung cancer.Chinese medicine · 2023Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Single-copy loss-of-function mutations in the progranulin gene (PGRN) underlie the neurodegenerative disease frontotemporal lobar degeneration, while homozygous loss-of-function of PGRN results in the lysosomal storage disorder neuronal ceroid lipofuscinosis. Despite evidence that normal PGRN levels are critical for neuronal health, the function of this protein is not yet understood. Here, we show that PGRN stimulates the in vitro maturation of the lysosomal aspartyl protease cathepsin D (CTSD). CTSD is delivered to the endolysosomal system as an inactive precursor (proCTSD) and requires sequential cleavage steps via intermediate forms to achieve the mature state (matCTSD). In co-immunoprecipitation experiments, PGRN interacts predominantly with immature pro- and intermediate forms of CTSD. PGRN enhances in vitro conversion of proCTSD to matCTSD in a concentration-dependent manner. Differential scanning fluorimetry shows a destabilizing effect induced by PGRN on proCTSD folding (∆T
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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.