Reducing acetylated tau is neuroprotective in brain injury

Min Kyoo Shin; Edwin Vázquez-Rosa; Yeojung Koh; Matasha Dhar; Kalyani Chaubey; Coral J. Cintrón-Pérez; Sarah Barker; Emiko Miller; Kathryn Franke; Maria F. Noterman; Divya Seth; Rachael S. Allen; Cara T. Motz; Sriganesh Ramachandra Rao; Lara A. Skelton; Machelle T. Pardue; Steven J. Fliesler; Chao Wang; Tara E. Tracy; Li Gan; Daniel J. Liebl; Jude P.J. Savarraj; Glenda L. Torres; Hilda Ahnstedt; Louise D. McCullough; Ryan S. Kitagawa; H. Alex Choi; Pengyue Zhang; Yuan Hou; Chien Wei Chiang; Lang Li; Francisco Ortiz; Jessica A. Kilgore; Noelle S. Williams; Victoria C. Whitehair; Tamar Gefen; Margaret E. Flanagan; Jonathan S. Stamler; Mukesh K. Jain; Allison Kraus; Feixiong Cheng; James D. Reynolds; Andrew A. Pieper

doi:10.1016/j.cell.2021.03.032

Reducing acetylated tau is neuroprotective in brain injury

Min Kyoo Shin, Edwin Vázquez-Rosa, Yeojung Koh, Matasha Dhar, Kalyani Chaubey, Coral J. Cintrón-Pérez, Sarah Barker, Emiko Miller, Kathryn Franke, Maria F. Noterman, Divya Seth, Rachael S. Allen, Cara T. Motz, Sriganesh Ramachandra Rao, Lara A. Skelton, Machelle T. Pardue, Steven J. Fliesler, Chao Wang, Tara E. Tracy, Li GanDaniel J. Liebl, Jude P.J. Savarraj, Glenda L. Torres, Hilda Ahnstedt, Louise D. McCullough, Ryan S. Kitagawa, H. Alex Choi, Pengyue Zhang, Yuan Hou, Chien Wei Chiang, Lang Li, Francisco Ortiz, Jessica A. Kilgore, Noelle S. Williams, Victoria C. Whitehair, Tamar Gefen, Margaret E. Flanagan, Jonathan S. Stamler, Mukesh K. Jain, Allison Kraus, Feixiong Cheng, James D. Reynolds, Andrew A. Pieper

Producción científica: Article › revisión exhaustiva

135 Citas (Scopus)

Resumen

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.

Idioma original	English (US)
Páginas (desde-hasta)	2715-2732.e23
Publicación	Cell
Volumen	184
N.º	10
DOI	https://doi.org/10.1016/j.cell.2021.03.032
Estado	Published - may 13 2021
Publicado de forma externa	Sí

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.cell.2021.03.032

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Shin, M. K., Vázquez-Rosa, E., Koh, Y., Dhar, M., Chaubey, K., Cintrón-Pérez, C. J., Barker, S., Miller, E., Franke, K., Noterman, M. F., Seth, D., Allen, R. S., Motz, C. T., Rao, S. R., Skelton, L. A., Pardue, M. T., Fliesler, S. J., Wang, C., Tracy, T. E., ... Pieper, A. A. (2021). Reducing acetylated tau is neuroprotective in brain injury. Cell, 184(10), 2715-2732.e23. https://doi.org/10.1016/j.cell.2021.03.032

Shin, MK, Vázquez-Rosa, E, Koh, Y, Dhar, M, Chaubey, K, Cintrón-Pérez, CJ, Barker, S, Miller, E, Franke, K, Noterman, MF, Seth, D, Allen, RS, Motz, CT, Rao, SR, Skelton, LA, Pardue, MT, Fliesler, SJ, Wang, C, Tracy, TE, Gan, L, Liebl, DJ, Savarraj, JPJ, Torres, GL, Ahnstedt, H, McCullough, LD, Kitagawa, RS, Choi, HA, Zhang, P, Hou, Y, Chiang, CW, Li, L, Ortiz, F, Kilgore, JA, Williams, NS, Whitehair, VC, Gefen, T, Flanagan, ME, Stamler, JS, Jain, MK, Kraus, A, Cheng, F, Reynolds, JD & Pieper, AA 2021, 'Reducing acetylated tau is neuroprotective in brain injury', Cell, vol. 184, n.º 10, pp. 2715-2732.e23. https://doi.org/10.1016/j.cell.2021.03.032

@article{51b0efc1931f4f2884dd24ec6e19291a,

title = "Reducing acetylated tau is neuroprotective in brain injury",

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.",

keywords = "Alzheimer's disease, P7C3, acetylation, congenital muscular dystrophy, diflunisal, neurodegeneration, neuroprotection, omigapil, salsalate, tau, traumatic brain injury",

author = "Shin, {Min Kyoo} and Edwin V{\'a}zquez-Rosa and Yeojung Koh and Matasha Dhar and Kalyani Chaubey and Cintr{\'o}n-P{\'e}rez, {Coral J.} and Sarah Barker and Emiko Miller and Kathryn Franke and Noterman, {Maria F.} and Divya Seth and Allen, {Rachael S.} and Motz, {Cara T.} and Rao, {Sriganesh Ramachandra} and Skelton, {Lara A.} and Pardue, {Machelle T.} and Fliesler, {Steven J.} and Chao Wang and Tracy, {Tara E.} and Li Gan and Liebl, {Daniel J.} and Savarraj, {Jude P.J.} and Torres, {Glenda L.} and Hilda Ahnstedt and McCullough, {Louise D.} and Kitagawa, {Ryan S.} and Choi, {H. Alex} and Pengyue Zhang and Yuan Hou and Chiang, {Chien Wei} and Lang Li and Francisco Ortiz and Kilgore, {Jessica A.} and Williams, {Noelle S.} and Whitehair, {Victoria C.} and Tamar Gefen and Flanagan, {Margaret E.} and Stamler, {Jonathan S.} and Jain, {Mukesh K.} and Allison Kraus and Feixiong Cheng and Reynolds, {James D.} and Pieper, {Andrew A.}",

note = "Publisher Copyright: {\textcopyright} 2021",

year = "2021",

month = may,

day = "13",

doi = "10.1016/j.cell.2021.03.032",

language = "English (US)",

volume = "184",

pages = "2715--2732.e23",

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T1 - Reducing acetylated tau is neuroprotective in brain injury

AU - Shin, Min Kyoo

AU - Vázquez-Rosa, Edwin

AU - Koh, Yeojung

AU - Dhar, Matasha

AU - Chaubey, Kalyani

AU - Cintrón-Pérez, Coral J.

AU - Barker, Sarah

AU - Miller, Emiko

AU - Franke, Kathryn

AU - Noterman, Maria F.

AU - Seth, Divya

AU - Allen, Rachael S.

AU - Motz, Cara T.

AU - Rao, Sriganesh Ramachandra

AU - Skelton, Lara A.

AU - Pardue, Machelle T.

AU - Fliesler, Steven J.

AU - Wang, Chao

AU - Tracy, Tara E.

AU - Gan, Li

AU - Liebl, Daniel J.

AU - Savarraj, Jude P.J.

AU - Torres, Glenda L.

AU - Ahnstedt, Hilda

AU - McCullough, Louise D.

AU - Kitagawa, Ryan S.

AU - Choi, H. Alex

AU - Zhang, Pengyue

AU - Hou, Yuan

AU - Chiang, Chien Wei

AU - Li, Lang

AU - Ortiz, Francisco

AU - Kilgore, Jessica A.

AU - Williams, Noelle S.

AU - Whitehair, Victoria C.

AU - Gefen, Tamar

AU - Flanagan, Margaret E.

AU - Stamler, Jonathan S.

AU - Jain, Mukesh K.

AU - Kraus, Allison

AU - Cheng, Feixiong

AU - Reynolds, James D.

AU - Pieper, Andrew A.

PY - 2021/5/13

Y1 - 2021/5/13

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - P7C3

KW - acetylation

KW - congenital muscular dystrophy

KW - diflunisal

KW - neurodegeneration

KW - neuroprotection

KW - omigapil

KW - salsalate

KW - tau

KW - traumatic brain injury

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UR - http://www.scopus.com/inward/citedby.url?scp=85104992839&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2021.03.032

DO - 10.1016/j.cell.2021.03.032

M3 - Article

C2 - 33852912

AN - SCOPUS:85104992839

SN - 0092-8674

VL - 184

SP - 2715-2732.e23

JO - Cell

JF - Cell

IS - 10

ER -

Reducing acetylated tau is neuroprotective in brain injury

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ASJC Scopus subject areas

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