Pin1 affects Tau phosphorylation in response to Abeta oligomers.
Mol Cell Neurosci
; 42(1): 75-80, 2009 Sep.
Article
en En
| MEDLINE
| ID: mdl-19520166
ABSTRACT
We show that in hippocampal cultured neurons, dephosphorylation of peptidyl-prolyl cis-trans isomerase Pin1 on Ser16 is occurring during the early stages of exposure to Abeta (1-42) oligomers. This occurrence, resulting in Pin1 activation, is paralleled by Tau(Thr231) dephosphorylation, probably due to Pin1-mediated Tau isomerisation. Indeed, in the presence of the specific Pin1 inhibitor juglone, Abeta-induced Tau(Thr231)dephosphorylation is prevented. The involvement of protein phosphatase 2A (PP2A) in dephosphorylation of isomerised Tau is shown by the co-treatment of neurons with Abeta (1-42) and okadaic acid, a PP2A inhibitor, leading to Tau(Thr231) hyperphosphorylation. We also report the modulation, via Pin1, of Ser199, Ser396, Ser400 and Ser404 phosphorylation state in response to Abeta treatment. Taken together, these data suggest for the first time that an early Pin1 response might be transiently evoked by Abeta 1-42 oligomers, preventing Tau hyperphosphorylation. This evidence highlights the role of Pin1 as Tau phosphorylation modulator during Alzheimer onset.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Fragmentos de Péptidos
/
Péptidos beta-Amiloides
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Proteínas tau
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Proteínas Adaptadoras Transductoras de Señales
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Neuronas
Límite:
Animals
Idioma:
En
Revista:
Mol Cell Neurosci
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEUROLOGIA
Año:
2009
Tipo del documento:
Article
País de afiliación:
Italia