ArticleProceedings of the National Academy of Sciences of the United States of America2021
Developmental synaptic regulator, TWEAK/Fn14 signaling, is a determinant of synaptic function in models of stroke and neurodegeneration.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 35 citations in OpenAlex.
- SIRT1 in brain aging: molecular mechanisms and therapeutic potential of pharmacological and natural modulators.Biogerontology · 2026Review
- Restoring RCAN1 dosage mitigates sleep and EEG abnormalities in a Down syndrome model.Neurobiology of disease · 2026Article
- SIRT1 Activators as Geroprotective Agents in Brain Aging: Mechanisms and Therapeutic Potential.Neuromolecular medicine · 2026Review
- Proteomics signatures associated with cognitive trajectories: evidence from the English Longitudinal Study of Ageing.medRxiv : the preprint server for health sciences · 2026Article
- Fn14 is an activity-dependent, Bmal1-regulated cytokine receptor that induces rod-like microglia and restricts neuronal activity in vivo.Cell reports · 2026Article
- Time‑resolved multi-omic analysis of paclitaxel exposure in human iPSC‑derived sensory neurons unveils mechanisms of chemotherapy‑induced peripheral neuropathy.Cell death & disease · 2026Article
- Soluble immune factor profiles in blood and CSF associated with LRRK2 mutations and Parkinson's disease.NPJ Parkinson's disease · 2025Article
- Aurintricarboxylic Acid Attenuates Tramadol Withdrawal Syndrome Via TWEAK/FN14 Inhibition and CREB Modulation in Mice Model.Neuromolecular medicine · 2025Article
- Experience-dependent control of synaptic remodeling and structural plasticity by glia.Current opinion in neurobiology · 2025Review
- Changes in Neuroimmunological Synapses During Cerebral Ischemia.Translational stroke research · 2025Review
- Crumbling Pathogenesis and Biomarkers for Diabetic Peripheral Neuropathy.Biomedicines · 2025Review
- Synaptic Pruning by Microglia: Lessons from Genetic Studies in Mice.Developmental neuroscience · 2025Review
- TWEAK-Fn14: a promising target for cardio-cerebrovascular diseases and brain-heart syndrome.Frontiers in immunology · 2025Review
- Current evidence of synaptic dysfunction after stroke: Cellular and molecular mechanisms.CNS neuroscience & therapeutics · 2024Review
- The cytokine receptor Fn14 is a molecular brake on neuronal activity that mediates circadian functionbioRxiv : the preprint server for biology · 2024Article
- Review
- Review
- Targeted ablation of Fn14 receptor improves exercise capacity and inhibits neurogenic muscle atrophy.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- ISGylation is induced in neurons by demyelination driving ISG15-dependent microglial activation.Journal of neuroinflammation · 2022Article
- Proteolytically generated soluble Tweak Receptor Fn14 is a blood biomarker for γ-secretase activity.EMBO molecular medicine · 2022Article
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Identifying molecular mediators of neural circuit development and/or function that contribute to circuit dysfunction when aberrantly reengaged in neurological disorders is of high importance. The role of the TWEAK/Fn14 pathway, which was recently reported to be a microglial/neuronal axis mediating synaptic refinement in experience-dependent visual development, has not been explored in synaptic function within the mature central nervous system. By combining electrophysiological and phosphoproteomic approaches, we show that TWEAK acutely dampens basal synaptic transmission and plasticity through neuronal Fn14 and impacts the phosphorylation state of pre- and postsynaptic proteins in adult mouse hippocampal slices. Importantly, this is relevant in two models featuring synaptic deficits. Blocking TWEAK/Fn14 signaling augments synaptic function in hippocampal slices from amyloid-beta-overexpressing mice. After stroke, genetic or pharmacological inhibition of TWEAK/Fn14 signaling augments basal synaptic transmission and normalizes plasticity. Our data support a glial/neuronal axis that critically modifies synaptic physiology and pathophysiology in different contexts in the mature brain and may be a therapeutic target for improving neurophysiological outcomes.
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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.