ArticleNature communications2018
Targeting Tyro3 ameliorates a model of PGRN-mutant FTLD-TDP via tau-mediated synaptic pathology.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 32 citations in OpenAlex.
- CDK3 induces neuronal death and brain atrophy in Alzheimer's disease.Nature aging · 2026Article
- Opposing role of phagocytic receptors MERTK and AXL in Progranulin deficient FTD.Communications biology · 2025Article
- Biochemical, Biomarker, and Behavioral Characterization of the GrnMolecular neurobiology · 2024Article
- Biochemical, biomarker, and behavioral characterization of thebioRxiv : the preprint server for biology · 2024Article
- Tyro3 promotes the maturation of glutamatergic synapses.Frontiers in neuroscience · 2024Article
- Preoperative cerebrospinal fluid biomarkers may be associated with postoperative delirium in patients undergoing knee/hip arthroplasty: the PNDABLE study.BMC geriatrics · 2023Article
- Progranulin deficiency suppresses allergic asthma and enhances efferocytosis via PPAR-γ/MFG-E8 regulation in macrophages.Immunity, inflammation and disease · 2023Article
- cPKCγ Deficiency Exacerbates Autophagy Impairment and Hyperphosphorylated Tau Buildup through the AMPK/mTOR Pathway in Mice with Type 1 Diabetes Mellitus.Neuroscience bulletin · 2022Article
- The role of PKC/PKR in aging, Alzheimer's disease, and perioperative neurocognitive disorders.Frontiers in aging neuroscience · 2022Article
- HMGB1 signaling phosphorylates Ku70 and impairs DNA damage repair in Alzheimer's disease pathology.Communications biology · 2021Article
- Loss of Lysosomal Proteins Progranulin and Prosaposin Associated with Increased Neurofibrillary Tangle Development in Alzheimer Disease.Journal of neuropathology and experimental neurology · 2021Article
- Prediction and verification of the AD-FTLD common pathomechanism based on dynamic molecular network analysis.Communications biology · 2021Article
- DNA damage in embryonic neural stem cell determines FTLDs' fate via early-stage neuronal necrosis.Life science alliance · 2021Article
- Neuropathological and behavioral characterization of aged Grn R493X progranulin-deficient frontotemporal dementia knockin mice.Acta neuropathologica communications · 2021Article
- Abnormal phosphorylation of tau protein and neuroinflammation induced by laparotomy in an animal model of postoperative delirium.Experimental brain research · 2021Article
- Lysosomal Dysfunction and Other Pathomechanisms in FTLD: Evidence from Progranulin Genetics and Biology.Advances in experimental medicine and biology · 2021Article
- Approaches to develop therapeutics to treat frontotemporal dementia.Neuropharmacology · 2020Review
- Kinome profiling of non-Hodgkin lymphoma identifies Tyro3 as a therapeutic target in primary effusion lymphoma.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- TYRO3: A potential therapeutic target in cancer.Experimental biology and medicine (Maywood, N.J.) · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in the progranulin (PGRN) gene cause a tau pathology-negative and TDP43 pathology-positive form of frontotemporal lobar degeneration (FTLD-TDP). We generated a knock-in mouse harboring the R504X mutation (PGRN-KI). Phosphoproteomic analysis of this model revealed activation of signaling pathways connecting PKC and MAPK to tau prior to TDP43 aggregation and cognitive impairments, and identified PKCα as the kinase responsible for the early-stage tau phosphorylation at Ser203. Disinhibition of Gas6 binding to Tyro3 due to PGRN reduction results in activation of PKCα via PLCγ, inducing tau phosphorylation at Ser203, mislocalization of tau to dendritic spines, and spine loss. Administration of a PKC inhibitor, B-Raf inhibitor, or knockdown of molecules in the Gas6-Tyro3-tau axis rescues spine loss and cognitive impairment of PGRN-KI mice. Collectively, these results suggest that targeting of early-stage and aggregation-independent tau signaling represents a promising therapeutic strategy for this disease.
Indexed as
Identifiers
What OpenQuestion holds
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.