Secretion of long Abeta-related peptides processed at epsilon-cleavage site is dependent on the alpha-secretase pre-cutting |
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Authors: | Kametani Fuyuki |
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Institution: | Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagayaku, Tokyo 156-8585, Japan. kametani@prit.go.jp |
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Abstract: | Abeta is the major component of amyloid in the brain in Alzheimer's disease and is derived from Alzheimer amyloid precursor protein (APP) by sequential proteolytic cleavage involving alpha-, beta- and gamma-secretase. Recently, gamma-secretase was shown to cleave near the cytoplasmic membrane boundary of APP (called the epsilon-cleavage), as well as in the middle of the membrane domain (gamma-cleavage). However, the precise relationship between gamma- and epsilon-cleavage is still unknown. In this paper, I analyzed Abeta-related peptides using immunoprecipitation and liquid chromatography ion trap mass spectrometer and found some long Abeta-related peptides, starting at Abeta residues 16Lys-23Asp and ending at 43Thr-52Leu, in the culture media of COS-1 cells and in human brain extract. These results indicated that longer Abeta-related peptides cleaved at epsilon-cleavage site were secreted under normal conditions and were dependent on the alpha-secretase cleavage products. |
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Keywords: | Amyloid precursor protein Amyloid Aβ γ -Secretase ε -Cleavage LC/MS/MS |
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