Aβ(1-42) inhibition of LTP is mediated by a signaling pathway involving caspase-3, Akt1 and GSK-3β

• Published in: Nature neuroscience Vol. 14; no. 5; pp. 545 - 547
• Main Authors: Jo, Jihoon, Whitcomb, Daniel J, Olsen, Kimberly Moore, Kerrigan, Talitha L, Lo, Shih-Ching, Bru-Mercier, Gilles, Dickinson, Bryony, Scullion, Sarah, Sheng, Morgan, Collingridge, Graham, Cho, Kwangwook
• Format: Journal Article
• Language: English
• Published: United States 01.05.2011
• Subjects: Amyloid beta-Peptides - pharmacology; Animals; Animals, Newborn; Biophysics; Caspase 3 - deficiency; Caspase 3 - metabolism; Electric Stimulation - methods; Enzyme Inhibitors - pharmacology; Glycogen Synthase Kinase 3 - genetics; Glycogen Synthase Kinase 3 - metabolism; Glycogen Synthase Kinase 3 beta; Green Fluorescent Proteins - genetics; Hippocampus - cytology; Hippocampus - drug effects; Hippocampus - physiology; Long-Term Potentiation - drug effects; Long-Term Potentiation - genetics; Mice; Mice, Knockout; Neurons - drug effects; Neurons - metabolism; Organ Culture Techniques; Patch-Clamp Techniques; Peptide Fragments - pharmacology; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; Pyridines - pharmacology; Pyrimidines - pharmacology; Rats; Rats, Wistar; Signal Transduction - drug effects; Signal Transduction - genetics; Signal Transduction - physiology; Transfection - methods; X-Linked Inhibitor of Apoptosis Protein - genetics
• ISSN: 1546-1726
• DOI: 10.1038/nn.2785

Amyloid-β(1-42) (Aβ) is thought to be a major mediator of the cognitive deficits in Alzheimer's disease. The ability of Aβ to inhibit hippocampal long-term potentiation provides a cellular correlate of this action, but the underlying molecular mechanism is only partially understood. We found that a signaling pathway involving caspase-3, Akt1 and glycogen synthase kinase-3β is an important mediator of this effect in rats and mice.