Morin attenuates tau hyperphosphorylation by inhibiting GSK3β
Alzheimer's disease (AD) is the major form of age-related dementia and is characterized by progressive cognitive impairment, the accumulation of extracellular amyloid β-peptide (Aβ), and intracellular hyperphosphorylated tau aggregates in affected brain regions. Tau hyperphosphorylation and acc...
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doaj-c5c13fd475ea46b2bbbb0154087746c32021-03-22T12:37:16ZengElsevierNeurobiology of Disease1095-953X2011-11-01442223230Morin attenuates tau hyperphosphorylation by inhibiting GSK3βEun Ji Gong0Hee Ra Park1Mi Eun Kim2Shunfu Piao3Eunjin Lee4Dong-Gyu Jo5Hae Young Chung6Nam-Chul Ha7Mark P. Mattson8Jaewon Lee9Department of Pharmacy, College of Pharmacy and Research Institute for Drug Development, Longevity Life Science and Technology Institutes, Pusan National University, Geumjeong-gu, Busan 609-735, Republic of KoreaDepartment of Pharmacy, College of Pharmacy and Research Institute for Drug Development, Longevity Life Science and Technology Institutes, Pusan National University, Geumjeong-gu, Busan 609-735, Republic of KoreaDepartment of Pharmacy, College of Pharmacy and Research Institute for Drug Development, Longevity Life Science and Technology Institutes, Pusan National University, Geumjeong-gu, Busan 609-735, Republic of KoreaDepartment of Pharmacy, College of Pharmacy and Research Institute for Drug Development, Longevity Life Science and Technology Institutes, Pusan National University, Geumjeong-gu, Busan 609-735, Republic of KoreaDepartment of Pharmacy, College of Pharmacy and Research Institute for Drug Development, Longevity Life Science and Technology Institutes, Pusan National University, Geumjeong-gu, Busan 609-735, Republic of KoreaCollege of Pharmacy, Sungkyunkwan University, Suwon, Republic of KoreaDepartment of Pharmacy, College of Pharmacy and Research Institute for Drug Development, Longevity Life Science and Technology Institutes, Pusan National University, Geumjeong-gu, Busan 609-735, Republic of KoreaDepartment of Pharmacy, College of Pharmacy and Research Institute for Drug Development, Longevity Life Science and Technology Institutes, Pusan National University, Geumjeong-gu, Busan 609-735, Republic of KoreaLaboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD, USADepartment of Pharmacy, College of Pharmacy and Research Institute for Drug Development, Longevity Life Science and Technology Institutes, Pusan National University, Geumjeong-gu, Busan 609-735, Republic of Korea; Corresponding author at: Department of Pharmacy, College of Pharmacy, Longevity Life Science and Technology Institutes, Pusan National University, Geumjeong-gu, Busan, 609-735, South Korea. Fax: +82 51 513 6754.Alzheimer's disease (AD) is the major form of age-related dementia and is characterized by progressive cognitive impairment, the accumulation of extracellular amyloid β-peptide (Aβ), and intracellular hyperphosphorylated tau aggregates in affected brain regions. Tau hyperphosphorylation and accumulation in neurofibrillary tangles is strongly correlated with cognitive deficits, and is apparently a critical event in the dementia process because mutations in tau can cause a tangle-only form of dementia called frontotemporal lobe dementia. Among kinases that phosphorylate tau, glycogen synthase kinase 3β (GSK3β) is strongly implicated in AD pathogenesis. In the present study, we established an ELISA to screen for agents that inhibit GSK3β activity and found that the flavonoid morin effectively inhibited GSK3β activity and blocked GSK3β-induced tau phosphorylation in vitro. In addition, morin attenuated Aβ-induced tau phosphorylation and protected human neuroblastoma cells against Aβ cytotoxicity. Furthermore, treatment of 3xTg-AD mice with morin resulted in reductions in tau hyperphosphorylation and paired helical filament-like immunoreactivity in hippocampal neurons. Morin is a novel inhibitor of GSK3β that can reduce tau pathology in vivo and may have potential as a therapeutic agent in tauopathies.http://www.sciencedirect.com/science/article/pii/S0969996111002312Alzheimer's diseaseGSK3βTau hyperphosphorylationMorin |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Eun Ji Gong Hee Ra Park Mi Eun Kim Shunfu Piao Eunjin Lee Dong-Gyu Jo Hae Young Chung Nam-Chul Ha Mark P. Mattson Jaewon Lee |
spellingShingle |
Eun Ji Gong Hee Ra Park Mi Eun Kim Shunfu Piao Eunjin Lee Dong-Gyu Jo Hae Young Chung Nam-Chul Ha Mark P. Mattson Jaewon Lee Morin attenuates tau hyperphosphorylation by inhibiting GSK3β Neurobiology of Disease Alzheimer's disease GSK3β Tau hyperphosphorylation Morin |
author_facet |
Eun Ji Gong Hee Ra Park Mi Eun Kim Shunfu Piao Eunjin Lee Dong-Gyu Jo Hae Young Chung Nam-Chul Ha Mark P. Mattson Jaewon Lee |
author_sort |
Eun Ji Gong |
title |
Morin attenuates tau hyperphosphorylation by inhibiting GSK3β |
title_short |
Morin attenuates tau hyperphosphorylation by inhibiting GSK3β |
title_full |
Morin attenuates tau hyperphosphorylation by inhibiting GSK3β |
title_fullStr |
Morin attenuates tau hyperphosphorylation by inhibiting GSK3β |
title_full_unstemmed |
Morin attenuates tau hyperphosphorylation by inhibiting GSK3β |
title_sort |
morin attenuates tau hyperphosphorylation by inhibiting gsk3β |
publisher |
Elsevier |
series |
Neurobiology of Disease |
issn |
1095-953X |
publishDate |
2011-11-01 |
description |
Alzheimer's disease (AD) is the major form of age-related dementia and is characterized by progressive cognitive impairment, the accumulation of extracellular amyloid β-peptide (Aβ), and intracellular hyperphosphorylated tau aggregates in affected brain regions. Tau hyperphosphorylation and accumulation in neurofibrillary tangles is strongly correlated with cognitive deficits, and is apparently a critical event in the dementia process because mutations in tau can cause a tangle-only form of dementia called frontotemporal lobe dementia. Among kinases that phosphorylate tau, glycogen synthase kinase 3β (GSK3β) is strongly implicated in AD pathogenesis. In the present study, we established an ELISA to screen for agents that inhibit GSK3β activity and found that the flavonoid morin effectively inhibited GSK3β activity and blocked GSK3β-induced tau phosphorylation in vitro. In addition, morin attenuated Aβ-induced tau phosphorylation and protected human neuroblastoma cells against Aβ cytotoxicity. Furthermore, treatment of 3xTg-AD mice with morin resulted in reductions in tau hyperphosphorylation and paired helical filament-like immunoreactivity in hippocampal neurons. Morin is a novel inhibitor of GSK3β that can reduce tau pathology in vivo and may have potential as a therapeutic agent in tauopathies. |
topic |
Alzheimer's disease GSK3β Tau hyperphosphorylation Morin |
url |
http://www.sciencedirect.com/science/article/pii/S0969996111002312 |
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