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Reducing acetylated tau is neuroprotective in brain injury.
Shin, Min-Kyoo; Vázquez-Rosa, Edwin; Koh, Yeojung; Dhar, Matasha; Chaubey, Kalyani; Cintrón-Pérez, Coral J; Barker, Sarah; Miller, Emiko; Franke, Kathryn; Noterman, Maria F; Seth, Divya; Allen, Rachael S; Motz, Cara T; Rao, Sriganesh Ramachandra; Skelton, Lara A; Pardue, Machelle T; Fliesler, Steven J; Wang, Chao; Tracy, Tara E; Gan, Li; Liebl, Daniel J; Savarraj, Jude P J; Torres, Glenda L; Ahnstedt, Hilda; McCullough, Louise D; Kitagawa, Ryan S; Choi, H Alex; Zhang, Pengyue; Hou, Yuan; Chiang, Chien-Wei; Li, Lang; Ortiz, Francisco; Kilgore, Jessica A; Williams, Noelle S; Whitehair, Victoria C; Gefen, Tamar; Flanagan, Margaret E; Stamler, Jonathan S; Jain, Mukesh K; Kraus, Allison; Cheng, Feixiong; Reynolds, James D; Pieper, Andrew A.
Afiliación
  • Shin MK; Harrington 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 Mo
  • Vázquez-Rosa E; Harrington 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 Mo
  • Koh Y; Harrington 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 Mo
  • Dhar M; Harrington 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 Mo
  • Chaubey K; Harrington 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 Mo
  • Cintrón-Pérez CJ; Harrington 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 Mo
  • Barker S; Harrington 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 Mo
  • Miller E; Harrington 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 Mo
  • Franke K; Harrington 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 Mo
  • Noterman MF; Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
  • Seth D; 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.
  • Allen RS; Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Healthcare System, Atlanta, GA, USA; Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, US.
  • Motz CT; Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Healthcare System, Atlanta, GA, USA; Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, US.
  • Rao SR; Departments 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.
  • Skelton LA; Departments 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.
  • Pardue MT; Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Healthcare System, Atlanta, GA, USA; Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, US.
  • Fliesler SJ; Departments 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.
  • Wang C; Gladstone Institute of Neurological Disease, San Francisco, CA, USA.
  • Tracy TE; The Buck Institute, Novato, CA, USA.
  • Gan L; Helen and Robert Appel Alzheimer's Disease Research Institute, Weill Cornell Medicine, New York, NY, USA.
  • Liebl DJ; The Miami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL, USA.
  • Savarraj JPJ; Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.
  • Torres GL; Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.
  • Ahnstedt H; Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.
  • McCullough LD; Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.
  • Kitagawa RS; Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.
  • Choi HA; Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.
  • Zhang P; Department of Biomedical Informatics, College of Medicine, Ohio State University, Columbus, OH, USA.
  • Hou Y; Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
  • Chiang CW; Department of Biomedical Informatics, College of Medicine, Ohio State University, Columbus, OH, USA.
  • Li L; Department of Biomedical Informatics, College of Medicine, Ohio State University, Columbus, OH, USA.
  • Ortiz F; Department of Biochemistry, UT Southwestern Medical Center, Dallas, TX, USA.
  • Kilgore JA; Department of Biochemistry, UT Southwestern Medical Center, Dallas, TX, USA.
  • Williams NS; Department of Biochemistry, UT Southwestern Medical Center, Dallas, TX, USA.
  • Whitehair VC; MetroHealth Rehabilitation Institute, The MetroHealth System, Cleveland, OH; Department of Physical Medicine and Rehabilitation, Case Western Reserve University, School of Medicine, Cleveland, OH USA.
  • Gefen T; Department 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.
  • Flanagan ME; Mesulam 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.
  • Stamler JS; Harrington 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, Clevelan
  • Jain MK; Harrington Discovery Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, USA; Department of Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH, USA.
  • Kraus A; Department of Pathology, Case Western Reserve University, School of Medicine, Cleveland, OH, USA.
  • Cheng F; Genomic 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 U
  • Reynolds JD; Harrington 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 Hospital
  • Pieper AA; Harrington 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 Mo
Cell ; 184(10): 2715-2732.e23, 2021 05 13.
Article en En | MEDLINE | ID: mdl-33852912
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas tau / Enfermedad de Alzheimer / Neuroprotección / Lesiones Traumáticas del Encéfalo Tipo de estudio: Risk_factors_studies Límite: Animals / Female / Humans / Male Idioma: En Revista: Cell Año: 2021 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas tau / Enfermedad de Alzheimer / Neuroprotección / Lesiones Traumáticas del Encéfalo Tipo de estudio: Risk_factors_studies Límite: Animals / Female / Humans / Male Idioma: En Revista: Cell Año: 2021 Tipo del documento: Article Pais de publicación: Estados Unidos