16 research outputs found
Copolymers from a Single Monomer: Synthesis of Poly(methylidene-co-trimethylsilylmethylidene)
Catalytic Hydrosilylation Routes to Divinylbenzene Bridged Silole and Silafluorene Polymers. Applications to Surface Imaging of Explosive Particulates
The Interplay of Akt and ERK in Aβ Toxicity and Insulin-Mediated Protection in Primary Hippocampal Cell Culture
mTor Is a Signaling Hub in Cell Survival: A Mass-Spectrometry-Based Proteomics Investigation
The Insulin/Akt Signaling Pathway Is Targeted by Intracellular β-Amyloid
Intraneuronal β-amyloid (Aβi) accumulates early in Alzheimer's disease (AD) and inclusion body myositis. Several organelles, receptor molecules, homeostatic processes, and signal transduction components have been identified as sensitive to Aβ. Although prior studies implicate the insulin-PI3K-Akt signaling cascade, a specific step within this or any essential metabolic or survival pathway has not emerged as a molecular target. We tested the effect of Aβ42 on each component of this cascade. In AD brain, the association between PDK and Akt, phospho-Akt levels and its activity were all decreased relative to control. In cell culture, Aβi expression inhibited both insulin-induced Akt phosphorylation and activity. In vitro experiments identified that β-amyloid (Aβ), especially oligomer preparations, specifically interrupted the PDK-dependent activation of Akt. Aβi also blocked the association between PDK and Akt in cell-based and in vitro experiments. Importantly, Aβ did not interrupt Akt or PI3K activities (once stimulated) nor did it affect more proximal signal events. These results offer a novel therapeutic strategy to neutralize Aβ-induced energy failure and neuronal death