Serine Phosphorylation of IRS1 Correlates with Aß-Unrelated Memory Deficits and Elevation in Aß Level Prior to the Onset of Memory Decline in AD.
Nutrients
; 11(8)2019 Aug 17.
Article
en En
| MEDLINE
| ID: mdl-31426549
ABSTRACT
The biological effects of insulin signaling are regulated by the phosphorylation of insulin receptor substrate 1 (IRS1) at serine (Ser) residues. In the brain, phosphorylation of IRS1 at specific Ser sites increases in patients with Alzheimer's disease (AD) and its animal models. However, whether the activation of Ser sites on neural IRS1 is related to any type of memory decline remains unclear. Here, we show the modifications of IRS1 through its phosphorylation at etiology-specific Ser sites in various animal models of memory decline, such as diabetic, aged, and amyloid precursor protein (APP) knock-in NL-G-F (APPKINL-G-F) mice. Substantial phosphorylation of IRS1 at specific Ser sites occurs in type 2 diabetes- or age-related memory deficits independently of amyloid-ß (Aß). Furthermore, we present the first evidence that, in APPKINL-G-F mice showing Aß42 elevation, the increased phosphorylation of IRS1 at multiple Ser sites occurs without memory impairment. Our findings suggest that the phosphorylation of IRS1 at specific Ser sites is a potential marker of Aß-unrelated memory deficits caused by type 2 diabetes and aging; however, in Aß-related memory decline, the modifications of IRS1 may be a marker of early detection of Aß42 elevation prior to the onset of memory decline in AD.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Péptidos beta-Amiloides
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Precursor de Proteína beta-Amiloide
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Proteínas Sustrato del Receptor de Insulina
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Enfermedad de Alzheimer
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Insulina
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Memoria
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Trastornos de la Memoria
Tipo de estudio:
Etiology_studies
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Prognostic_studies
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Screening_studies
Idioma:
En
Revista:
Nutrients
Año:
2019
Tipo del documento:
Article