Neuroglobin attenuates Alzheimer-like tau hyperphosphorylation by activating Akt signaling.
J Neurochem
; 120(1): 157-64, 2012 Jan.
Article
en En
| MEDLINE
| ID: mdl-21496024
ABSTRACT
Neuroglobin (Ngb) is a recently identified member of hemoglobin family, distributed mainly in central and peripheral nervous systems. Recent studies suggest that Ngb can protect neural cells from ß-amyloid-induced toxicity in Alzheimer disease (AD). Hyperphosphorylation of tau is another characterized pathological hallmark in the AD brains; however, it is not reported whether Ngb also affects tau phosphorylation. In this study, we found that the level of Ngb was significantly reduced in Tg2576 mice (a recognized mouse model of AD) and TgMAPt mice, and the level of Ngb was negatively correlated with tau phosphorylation. Over-expression of Ngb attenuates tau hyperphosphorylation at multiple AD-related sites induced by up-regulation of glycogen synthase kinase-3ß (GSK-3ß), a crucial tau kinase. While Ngb activates Akt and thus inhibits GSK-3ß, simultaneously inhibition of Akt abolishes the effects of Ngb on GSK-3ß inhibition and tau hyperphosphorylation. Our data indicate that Ngb may attenuate tau hyperphosphorylation through activating Akt signaling pathway, implying a therapeutic target for AD.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Fosforilación
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Globinas
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Transducción de Señal
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Proteínas tau
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Proteínas Proto-Oncogénicas c-akt
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Enfermedad de Alzheimer
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Proteínas del Tejido Nervioso
Límite:
Animals
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Humans
Idioma:
En
Revista:
J Neurochem
Año:
2012
Tipo del documento:
Article
País de afiliación:
China