A mechanistic link between oxidative stress and membrane mediated amyloidogenesis revealed by infrared spectroscopy |
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Authors: | Hiroaki Komatsu |
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Affiliation: | The Departments of Pharmacology, Biochemistry and Biophysics, and Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA |
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Abstract: | The fully developed lesion of Alzheimer's disease is a dense plaque composed of fibrillar amyloid β-proteins (Aβ) with a characteristic and well-ordered β-sheet secondary structure. Because the incipient lesion most likely develops when these proteins are first induced to form β-sheet structure, it is important to understand factors that induced Aβ to adopt this conformation. In this review, we describe the application of polarized attenuated total internal reflection infrared FT-IR spectroscopy for characterizing the conformation, orientation, and rate of accumulation of Aβ on lipid membranes. We also describe the application and yield of linked analysis, whereby multiple spectra are fit simultaneously with component bands that are constrained to share common fitting parameters. Results have shown that membranes promote β-sheet formation under a variety of circumstances that may be significant to the pathogenesis of Alzheimer's disease. |
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Keywords: | AD, Alzheimer's disease Aβ, amyloid β proteins Aβ40, 40-residue Aβ Aβ42, 42-residue Aβ PATIR-FTIR, polarized attenuated total internal reflection-Fourier transform infrared ATIR-FTIR, unpolarized attenuated total internal reflection-Fourier transform infrared IR, infrared DTPA, diethylenetriaminepentaacetic acid MRM-ESI-LC/MS/MS, multiple reaction monitoring electrospray ionization liquid chromatography tandem mass spectrometry SAPC, 1-stearoyl-2-arachidonyl phosphatidylcholine DMPC, dimyristoyl phosphatidylcholine BHT, butylated hydroxytoluene GM1, Ganglioside GM1 HNE, 4-hydroxy-2-nonenal SAPCOX, oxidized SAPC |
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