RGD Reference Report - Evidence of Abeta- and transgene-dependent defects in ERK-CREB signaling in Alzheimer's models. - Rat Genome Database

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Evidence of Abeta- and transgene-dependent defects in ERK-CREB signaling in Alzheimer's models.

Authors: Ma, QL  Harris-White, ME  Ubeda, OJ  Simmons, M  Beech, W  Lim, GP  Teter, B  Frautschy, SA  Cole, GM 
Citation: Ma QL, etal., J Neurochem. 2007 Nov;103(4):1594-607. Epub 2007 Aug 30.
RGD ID: 10059609
Pubmed: PMID:17760871   (View Abstract at PubMed)
PMCID: PMC2527620   (View Article at PubMed Central)
DOI: DOI:10.1111/j.1471-4159.2007.04869.x   (Journal Full-text)

Extracellular-signal regulated kinase (ERK) signaling is critical for memory and tightly regulated by acute environmental stimuli. In Alzheimer disease transgenic models, active ERK is shown to first be increased, then later reduced, but whether these baseline changes reflect disruptions in ERK signaling is less clear. We investigated the influence of the familial Alzheimer's disease transgene APPsw and beta-amyloid peptide (Abeta) immunoneutralization on cannulation injury-associated (i.c.v. infusion) ERK activation. At both 12 and 22 months of age, the trauma-associated activation of ERK observed in Tg(-) mice was dramatically attenuated in Tg(+). In cortices of 22-month-old non-infused mice, a reduction in ERK activation was observed in Tg(+), relative to Tg(-) mice. Intracerebroventricular (i.c.v.) anti-Abeta infusion significantly increased phosphorylated ERK, its substrate cAMP-response element-binding protein (CREB) and a downstream target, the NMDA receptor subunit. We also demonstrated that Abeta oligomer decreased active ERK and subsequently active CREB in human neuroblastoma cells, which could be prevented by oligomer immunoneutralization. Abeta oligomers also inhibited active ERK and CREB in primary neurons, in addition to reducing the downstream post-synaptic protein NMDA receptor subunit. These effects were reversed by anti-oligomer. Our data strongly support the existence of an APPsw transgene-dependent and Abeta oligomer-mediated defect in regulation of ERK activation.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Alzheimer's disease treatmentISOCrebbp (Mus musculus)10059609; 10059609protein:increased phosphorylation:hippocampus:RGD 
Alzheimer's disease treatmentIEP 10059609protein:increased phosphorylation:hippocampus:RGD 

Objects Annotated

Genes (Rattus norvegicus)
Crebbp  (CREB binding protein)

Genes (Mus musculus)
Crebbp  (CREB binding protein)

Genes (Homo sapiens)
CREBBP  (CREB binding protein)


Additional Information