The PKR activator PACT is induced by Aß: involvement in Alzheimer's disease.
Brain Pathol
; 22(2): 219-29, 2012 Mar.
Article
en En
| MEDLINE
| ID: mdl-21790829
The neuropathological hallmarks of Alzheimer's disease (AD) include senile plaques made of Aß peptide, neurofibrillary tangles containing hyperphosphorylated tau protein and neuronal loss. The pro-apoptotic kinase PKR can be activated by Aß and can phosphorylate tau protein via GSK3ß kinase activation. The activated form of PKR (pPKR) accumulates in affected neurons and could participate in neuronal degeneration in AD. The mechanism of abnormal PKR activation in AD is not elucidated but could be linked to the PKR activator PACT. PACT stainings, and levels were assessed in the brains of AD patients and in APP/PS1 knock-in transgenic mice and in cell cultures exposed to stresses. We showed that PACT and pPKR colocalizations are enhanced in AD brains. Their levels are increased and correlated in AD and APP/PS1 knock-in mice brains. In human neuroblastoma cells exposed to Aß, tunicamycin or H2O2, PACT and pPKR concentrations are increased. PACT then PKR inhibitions indicate that PACT is upstream of PKR activation. Our findings demonstrate that PACT levels are enhanced in AD brains and could partly be caused by the action of Aß. In addition, PACT participates in PKR activation. The PACT-PKR pathway represents a potential link between Aß accumulation, PKR activation and tau phosphorylation.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Péptidos beta-Amiloides
/
Proteínas de Unión al ARN
/
EIF-2 Quinasa
/
Enfermedad de Alzheimer
Límite:
Aged
/
Aged80
/
Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Brain Pathol
Asunto de la revista:
CEREBRO
/
PATOLOGIA
Año:
2012
Tipo del documento:
Article
Pais de publicación:
Suiza