ArticleHuman molecular genetics2014
Targeted manipulation of the sortilin-progranulin axis rescues progranulin haploinsufficiency.
Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.
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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.
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.
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Who cites it
65 citing papers in PubMed, 1 synthesis or guideline pooled it, 140 citations in OpenAlex.
- Finding memo: versatile interactions of the VPS10p-Domain receptors in Alzheimer's disease.Molecular neurodegeneration · 2022Pooled it
- Integrative analysis of single-cell multi-omics reveals heterogeneity in piriform cortex principal neurons and their selective vulnerability in Alzheimer's disease.Clinical and translational medicine · 2026Article
- Synergistic cooperation between progranulin and Jak2/Stat3 signaling determines definitive myeloid cell fate.Cell reports · 2026Article
- Additive value of early-phase β-Amyloid-PET for the differential diagnosis of non-Alzheimer's disease dementia.NeuroImage. Clinical · 2026Article
- Autophagy-Lysosome Pathway Dysfunction in Neurodegeneration and Cancer: Mechanisms and Therapeutic Opportunities.International journal of molecular sciences · 2025Review
- Interaction of sortilin with apolipoprotein E3 enables neurons to use long-chain fatty acids as alternative metabolic fuel.Nature metabolism · 2025Article
- Targeting Granulin Haploinsufficiency in Frontotemporal Dementia: From Genetic Mechanisms to Therapeutics.International journal of molecular sciences · 2025Review
- PGRN Counteracts the Associations of Abnormal Tau Proteins with Neurodegeneration and Cognitive Decline in Non-demented Adults: A Longitudinal Study.Molecular neurobiology · 2025Article
- The role of endolysosomal progranulin and TMEM106B in neurodegenerative diseases.Molecular neurodegeneration · 2025Review
- Development of AL101 (GSK4527226), a progranulin-elevating monoclonal antibody, as a potential treatment for Alzheimer's disease.Alzheimer's research & therapy · 2025Article
- Progranulin's Protective Mechanisms and Therapeutic Potential in Cardiovascular Disease.Cells · 2025Review
- Alzheimer's Disease and Frontotemporal Dementia: A Review of Pathophysiology and Therapeutic Approaches.Journal of neuroscience research · 2025Review
- Frequency and Longitudinal Course of Behavioral and Neuropsychiatric Symptoms in Participants With Genetic Frontotemporal Dementia.Neurology · 2024Article
- Sortilin is associated with progranulin deficiency and autism-like behaviors in valproic acid-induced autism rats.CNS neuroscience & therapeutics · 2024Article
- PGRN is involved in macrophage M2 polarization regulation through TNFR2 in periodontitis.Journal of translational medicine · 2024Article
- Progranulin and neuropathological features of Alzheimer's disease: longitudinal study.Aging clinical and experimental research · 2024Article
- An anti-sortilin affibody-peptide fusion inhibits sortilin-mediated progranulin degradation.Frontiers in immunology · 2024Article
- Investigating the role and regulation of GPNMB in progranulin-deficient macrophages.Frontiers in immunology · 2024Article
- Interleukin-6 Induces Stem Cell Propagation through Liaison with the Sortilin-Progranulin Axis in Breast Cancer.Cancers · 2023Article
- Progranulin and GPNMB: interactions in endo-lysosome function and inflammation in neurodegenerative disease.Journal of neuroinflammation · 2023Review
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
Progranulin (GRN) mutations causing haploinsufficiency are a major cause of frontotemporal lobar degeneration (FTLD-TDP). Recent discoveries demonstrating sortilin (SORT1) is a neuronal receptor for PGRN endocytosis and a determinant of plasma PGRN levels portend the development of enhancers targeting the SORT1-PGRN axis. We demonstrate the preclinical efficacy of several approaches through which impairing PGRN's interaction with SORT1 restores extracellular PGRN levels. Our report is the first to demonstrate the efficacy of enhancing PGRN levels in iPSC neurons derived from frontotemporal dementia (FTD) patients with PGRN deficiency. We validate a small molecule preferentially increases extracellular PGRN by reducing SORT1 levels in various mammalian cell lines and patient-derived iPSC neurons and lymphocytes. We further demonstrate that SORT1 antagonists and a small-molecule binder of PGRN₅₈₈₋₅₉₃, residues critical for PGRN-SORT1 binding, inhibit SORT1-mediated PGRN endocytosis. Collectively, our data demonstrate that the SORT1-PGRN axis is a viable target for PGRN-based therapy, particularly in FTD-GRN patients.
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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.