Endomorphin-2, an endogenous tetrapeptide, protects against Abeta1-42 in vitro and in vivo

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Viktor SzegediBotond Penke

Abstract

The underlying cause of Alzheimer's disease (AD) is thought to be the beta-amyloid aggregates formed mainly by Abeta1-42 peptide. Protective pentapeptides [e.g., Leu-Pro-Phe-Phe-Asp (LPFFD)] have been shown to prevent neuronal toxicity of Abeta1-42 by arresting and reversing fibril formation. Here we report that an endogenous tetrapeptide, endomorphin-2 (End-2, amino acid sequence: YPFF), defends against Abeta1-42 induced neuromodulatory effects at the cellular level. Although End-2 does not interfere with the kinetics of Abeta fibrillogenesis according to transmission electron microscopic studies and quasielastic light scattering measurements, it binds to Abeta1-42 during aggregation, as revealed by tritium-labeled End-2 binding assay and circular dichroism measurements. The tetrapeptide attenuates the inhibitory effect on cellular redox activity of Abeta1-42 in a dose-dependent manner, as measured by 3-(4,5-dimethylthiazolyl-2)-2,-5-diphenyltetrazolium bromide (MTT) assay. In vitro and in vivo electrophysiological experiments show that End-2 also protects against the field excitatory postsynaptic potential attenuating and the NMDA-evoked response-enhancing effect of Abeta1-42. Studies using [D-Ala (2), N-Me-Phe (4), Gly (5)-o...Continue Reading

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Citations

Oct 5, 2011·The Journal of Biological Chemistry·Marino ConvertinoAmedeo Caflisch
Apr 25, 2012·Neuromolecular Medicine·Zhiyou Cai, Anna Ratka
Feb 24, 2009·The Journal of Physical Chemistry. B·Qitao ZhaoXiyun Guan
Apr 28, 2021·Journal of Chemical Theory and Computation·Alexander van Teijlingen, Tell Tuttle

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