ArticleCell2021
Reducing acetylated tau is neuroprotective in brain injury.
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Article in Cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 143 papers, 2 of them syntheses that pooled it.
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143citing papers in PubMed, 2 pooled it
21.4field-weighted citation impact, top 1% of its field
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Who cites it
143 citing papers in PubMed, 2 syntheses or guidelines pooled it, 212 citations in OpenAlex.
- P7C3 Compounds as Targeted Mitochondrial Therapeutics for Brain Disorders.CNS neuroscience & therapeutics · 2026Pooled it
- Exploring the biological basis of acupuncture treatment for traumatic brain injury: a review of evidence from animal models.Frontiers in cellular neuroscience · 2024Pooled it
- Ischemic Stroke and Traumatic Brain Injury: Epidemiology, Molecular Pathways, and Emerging Therapies.MedComm · 2026Review
- SIRT1 in Neurodegenerative Diseases: Molecular Mechanisms, Disease Relevance, and Therapeutic Potential.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- Injectable Supramolecular Hydrogel Encapsulating CRISPR-Engineered MSCs Drives Synergistic Neuroprotection and Functional Recovery After Traumatic Brain Injury.Advanced healthcare materials · 2026Article
- ROS-ATM-CBP axis-mediated PARP1 lactylation aggravates doxorubicin-induced cardiotoxicity.Clinical and translational medicine · 2026Article
- Advances in Alzheimer's disease: mechanistic insights and therapeutic targets.Science China. Life sciences · 2026Review
- Recent advances in Alzheimer's disease: From molecular mechanisms to therapeutic strategies.Cell · 2026Review
- Endothelial KLF4 depletion drives age-related neurovascular dysfunction and neuropsychiatric impairment.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Multi-omics and artificial intelligence for precision drug discovery and potential clinical applications.Signal transduction and targeted therapy · 2026Review
- Tau Ablation Rewires Brain Cell Programs in Health and Restores Function in Disease.bioRxiv : the preprint server for biology · 2026Article
- Reduced ULK1 links impaired autophagy and mitophagy to Alzheimer's disease pathology.Nature aging · 2026Article
- GFAP degradation in TBI: linking novel modified products to astrocyte pathology and patient outcome.Acta neuropathologica communications · 2026Article
- Co-Delivery of Ferrostatin-1 and M2 Macrophage-Derived Exosomal Signals via Engineered Hybrid Nanovesicles Enables Synergistic Neuroprotection in Traumatic Brain Injury.ACS applied materials & interfaces · 2026Article
- P7C3-A20 prevents whole brain radiotherapy-induced chronic hippocampal redox imbalance and neuropsychiatric impairment in mice.Redox biology · 2026Article
- Artificial microRNAs targeting tau enable post-symptomatic functional recovery in aged tauopathy mice.Molecular therapy. Nucleic acids · 2026Article
- Sex-specific effects of acetylation on tauopathy in aging htau mice.Scientific reports · 2026Article
- Targeting tau in Alzheimer's Disease: rationale, approach and challenges.Molecular neurodegeneration · 2026Review
- Hypothermia Alleviates TBI-Induced Tau Hyperphosphorylation Through RBM3-Dependent GSK-3β and AMPK Pathways.Neurocritical care · 2026Article
- Pharmacologic reversal of advanced Alzheimer's disease in mice and identification of potential therapeutic nodes in human brain.Cell reports. Medicine · 2026Article
83 more citing papers are in PubMed but not listed here.
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Authors and funding
43 authors at 15 institutions in 1 country.
Min-Kyoo ShinHarrington Discovery Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, USA; Department of Psychiatry, Case Western Reserve University, Cleveland, OH, USA; Geriatric Psychiatry, GRECC, Louis Stokes Cleveland VA Medical Center; Cleveland, OH, USA; Institute for Transformative Molecular Medicine, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.
Edwin Vázquez-RosaHarrington Discovery Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, USA; Department of Psychiatry, Case Western Reserve University, Cleveland, OH, USA; Geriatric Psychiatry, GRECC, Louis Stokes Cleveland VA Medical Center; Cleveland, OH, USA; Institute for Transformative Molecular Medicine, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.
Yeojung KohHarrington Discovery Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, USA; Department of Psychiatry, Case Western Reserve University, Cleveland, OH, USA; Geriatric Psychiatry, GRECC, Louis Stokes Cleveland VA Medical Center; Cleveland, OH, USA; Institute for Transformative Molecular Medicine, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.
Matasha DharHarrington Discovery Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, USA; Department of Psychiatry, Case Western Reserve University, Cleveland, OH, USA; Geriatric Psychiatry, GRECC, Louis Stokes Cleveland VA Medical Center; Cleveland, OH, USA; Institute for Transformative Molecular Medicine, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.
Kalyani ChaubeyHarrington Discovery Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, USA; Department of Psychiatry, Case Western Reserve University, Cleveland, OH, USA; Geriatric Psychiatry, GRECC, Louis Stokes Cleveland VA Medical Center; Cleveland, OH, USA; Institute for Transformative Molecular Medicine, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.
Coral J Cintrón-PérezHarrington Discovery Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, USA; Department of Psychiatry, Case Western Reserve University, Cleveland, OH, USA; Geriatric Psychiatry, GRECC, Louis Stokes Cleveland VA Medical Center; Cleveland, OH, USA; Institute for Transformative Molecular Medicine, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.
Sarah BarkerHarrington Discovery Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, USA; Department of Psychiatry, Case Western Reserve University, Cleveland, OH, USA; Geriatric Psychiatry, GRECC, Louis Stokes Cleveland VA Medical Center; Cleveland, OH, USA; Institute for Transformative Molecular Medicine, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.
Emiko MillerHarrington Discovery Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, USA; Department of Psychiatry, Case Western Reserve University, Cleveland, OH, USA; Geriatric Psychiatry, GRECC, Louis Stokes Cleveland VA Medical Center; Cleveland, OH, USA; Institute for Transformative Molecular Medicine, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.
Kathryn FrankeHarrington Discovery Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, USA; Department of Psychiatry, Case Western Reserve University, Cleveland, OH, USA; Geriatric Psychiatry, GRECC, Louis Stokes Cleveland VA Medical Center; Cleveland, OH, USA; Institute for Transformative Molecular Medicine, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.
Maria F NotermanDepartment of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
Divya SethInstitute for Transformative Molecular Medicine, School of Medicine, Case Western Reserve University, Cleveland, OH, USA; Department of Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH, USA.
Rachael S AllenCenter for Visual and Neurocognitive Rehabilitation, Atlanta VA Healthcare System, Atlanta, GA, USA; Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, US.
Cara T MotzCenter for Visual and Neurocognitive Rehabilitation, Atlanta VA Healthcare System, Atlanta, GA, USA; Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, US.
Sriganesh Ramachandra RaoDepartments of Ophthalmology and Biochemistry, and the Neuroscience Graduate Program, SUNY-University at Buffalo, Buffalo, NY, USA; Research Service, VA Western NY Healthcare System, Buffalo, NY, USA.
Lara A SkeltonDepartments of Ophthalmology and Biochemistry, and the Neuroscience Graduate Program, SUNY-University at Buffalo, Buffalo, NY, USA; Research Service, VA Western NY Healthcare System, Buffalo, NY, USA.
Machelle T PardueCenter for Visual and Neurocognitive Rehabilitation, Atlanta VA Healthcare System, Atlanta, GA, USA; Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, US.
Steven J FlieslerDepartments of Ophthalmology and Biochemistry, and the Neuroscience Graduate Program, SUNY-University at Buffalo, Buffalo, NY, USA; Research Service, VA Western NY Healthcare System, Buffalo, NY, USA.
Chao WangGladstone Institute of Neurological Disease, San Francisco, CA, USA.
Tara E TracyThe Buck Institute, Novato, CA, USA.
Li GanHelen and Robert Appel Alzheimer's Disease Research Institute, Weill Cornell Medicine, New York, NY, USA.
Daniel J LieblThe Miami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL, USA.
Jude P J SavarrajDepartment of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Glenda L TorresDepartment of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Hilda AhnstedtDepartment of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Louise D McCulloughDepartment of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Ryan S KitagawaDepartment of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.
H Alex ChoiDepartment of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Pengyue ZhangDepartment of Biomedical Informatics, College of Medicine, Ohio State University, Columbus, OH, USA.
Yuan HouGenomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
Chien-Wei ChiangDepartment of Biomedical Informatics, College of Medicine, Ohio State University, Columbus, OH, USA.
Lang LiDepartment of Biomedical Informatics, College of Medicine, Ohio State University, Columbus, OH, USA.
Francisco OrtizDepartment of Biochemistry, UT Southwestern Medical Center, Dallas, TX, USA.
Jessica A KilgoreDepartment of Biochemistry, UT Southwestern Medical Center, Dallas, TX, USA.
Noelle S WilliamsDepartment of Biochemistry, UT Southwestern Medical Center, Dallas, TX, USA.
Victoria C WhitehairMetroHealth Rehabilitation Institute, The MetroHealth System, Cleveland, OH; Department of Physical Medicine and Rehabilitation, Case Western Reserve University, School of Medicine, Cleveland, OH USA.
Tamar GefenDepartment of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; Mesulam Center for Cognitive Neurology and Alzheimer's Disease, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Margaret E FlanaganMesulam Center for Cognitive Neurology and Alzheimer's Disease, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; Department of Pathology, Northwestern University, Chicago, IL, USA.
Jonathan S StamlerHarrington Discovery Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, USA; Institute for Transformative Molecular Medicine, School of Medicine, Case Western Reserve University, Cleveland, OH, USA; Department of Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH, USA.
Mukesh K JainHarrington Discovery Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, USA; Department of Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH, USA.
Allison KrausDepartment of Pathology, Case Western Reserve University, School of Medicine, Cleveland, OH, USA.
Feixiong ChengGenomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA; Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH, USA.
James D ReynoldsHarrington Discovery Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, USA; Institute for Transformative Molecular Medicine, School of Medicine, Case Western Reserve University, Cleveland, OH, USA; Departments of Anesthesiology & Perioperative Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH, USA.
Andrew A PieperHarrington Discovery Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, USA; Department of Psychiatry, Case Western Reserve University, Cleveland, OH, USA; Geriatric Psychiatry, GRECC, Louis Stokes Cleveland VA Medical Center; Cleveland, OH, USA; Institute for Transformative Molecular Medicine, School of Medicine, Case Western Reserve University, Cleveland, OH, USA; Weill Cornell Autism Research Program, Weill Cornell Medicine of Cornell University, New York, NY, USA; Department of Neuroscience, Case Western Reserve University, School of Medicine, Cleveland, OH, USA. Electronic address: andrew.pieper@harringtondiscovery.org.
University Hospitals of Cleveland · USThe University of Texas Health Science Center at Houston · USGeorgia Institute of Technology · USSouthwestern Medical Center · USThe Ohio State University · USVA Western New York Healthcare System · USCleveland Clinic Lerner College of Medicine · USCornell University · USNorthwestern University · USBuck Institute for Research on Aging · USGladstone Institutes · USMetroHealth · USUniversity of Iowa · USUniversity of Miami · USUniversity School · US
Funding
University of Buffalo Clinical and Translational Science Institute - Supplement SchulyerUL1TR001412 · NCATS · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI MURPHY, TIMOTHY F · 2015 to 2024
$33.8MMEDICAL SCIENTIST TRAINING PROGRAMT32GM007250 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI HUANG, ALEX YEE-CHEN · 1985 to 2023
$33.4MNeuropathology CoreP30AG013854 · NIA · NORTHWESTERN UNIVERSITY AT CHICAGO · PI ROGALSKI, EMILY J · 1996 to 2020
$28.9MProject 3: MRI Imaging of Redox Active Fe Predicts GBM Responses to Pharmacological AscorbateP01CA217797 · NCI · UNIVERSITY OF IOWA · PI CULLEN, JOSEPH J · 2018 to 2022
$9.6MTRAINING PROGRAM IN FREE RADICAL AND RADIATION BIOLOGYT32CA078586 · NCI · UNIVERSITY OF IOWA · PI SPITZ, DOUGLAS ROBERT · 1999 to 2024
$5.7MTranslational Therapeutics CoreP30AG062428 · NIA · CLEVELAND CLINIC LERNER COM-CWRU · PI LEVERENZ, JAMES BRUCE · 2019 to 2020
$5.0MEndophenotype Network-based Approaches to Prediction and Population-based Validation of In Silico Drug Repurposing for Alzheimer's DiseaseR01AG066707 · NIA · CLEVELAND CLINIC LERNER COM-CWRU · PI Feixiong Cheng · 2020 to 2026
$4.9MStabilizing the Tripartite Synaptic Complex Following TBIR01NS098740 · NINDS · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI Joacir Graciolli Graciolli Cordeiro, Daniel Jon Liebl · 2017 to 2026
$4.7MClinical, Neuroanatomic, and Pathologic Signatures of FTLD-tau in Dementia Phenotypes - Diversity Supplement (Antwan Howard)R01AG062566 · NIA · NORTHWESTERN UNIVERSITY AT CHICAGO · PI GEFEN, TAMAR D · 2020 to 2024
$2.1Mnvestigating the role of neuroinflammation in Limbic-predominant age related TDP43 encephalopathyK08AG065463 · NIA · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI FLANAGAN, MARGARET E · 2020 to 2024
$816kSynaptic mechanisms of tau-mediated pathogenesis in human iPSC-derived neuronsK01AG057862 · NIA · J. DAVID GLADSTONE INSTITUTES · PI TRACY, TARA · 2018 to 2022
$626kPathogenic events triggered by tau acetylation in neurodegenerative tauopathyF32AG043301 · NIA · J. DAVID GLADSTONE INSTITUTES · PI TRACY, TARA · 2012 to 2014
$156kBLRD VA I01 BX002439NCATS NIH HHS UL1 TR001412NCI NIH HHS P01 CA217797NCI NIH HHS T32 CA078586NIA NIH HHS F32 AG043301NIA NIH HHS K01 AG057862NIA NIH HHS K08 AG065463NIA NIH HHS P30 AG013854NIA NIH HHS P30 AG062428NIA NIH HHS R01 AG062566NIA NIH HHS R01 AG066707NIGMS NIH HHS T32 GM007250NINDS NIH HHS R01 NS098740RRD VA IK2 RX002928
Abstract
Traumatic brain injury (TBI) is the largest non-genetic, non-aging related risk factor for Alzheimer's disease (AD). We report here that TBI induces tau acetylation (ac-tau) at sites acetylated also in human AD brain. This is mediated by S-nitrosylated-GAPDH, which simultaneously inactivates Sirtuin1 deacetylase and activates p300/CBP acetyltransferase, increasing neuronal ac-tau. Subsequent tau mislocalization causes neurodegeneration and neurobehavioral impairment, and ac-tau accumulates in the blood. Blocking GAPDH S-nitrosylation, inhibiting p300/CBP, or stimulating Sirtuin1 all protect mice from neurodegeneration, neurobehavioral impairment, and blood and brain accumulation of ac-tau after TBI. Ac-tau is thus a therapeutic target and potential blood biomarker of TBI that may represent pathologic convergence between TBI and AD. Increased ac-tau in human AD brain is further augmented in AD patients with history of TBI, and patients receiving the p300/CBP inhibitors salsalate or diflunisal exhibit decreased incidence of AD and clinically diagnosed TBI.
Indexed as
NeuroprotectionAcetylationAlzheimer DiseaseAnimalsAnti-Inflammatory Agents, Non-SteroidalBiomarkersBrain Injuries, TraumaticCell LineDiflunisalFemaleGlyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)HumansMaleMiceMice, Inbred C57BLNeuronsAnti-Inflammatory Agents, Non-SteroidalBiomarkersDiflunisalGlyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)p300-CBP-Associated Factorp300-CBP Transcription FactorsSalicylatessalicylsalicylic acidSirtuin 1tau ProteinsacetylationAlzheimer’s diseasecongenital muscular dystrophydiflunisalneurodegenerationneuroprotectionomigapilP7C3salsalatetautraumatic brain injury
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