Secretion of long Abeta-related peptides processed at epsilon-cleavage site is dependent on the alpha-secretase pre-cutting

FEBS Letters
F Kametani

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.

References

Jun 6, 2002·Proceedings of the National Academy of Sciences of the United States of America·Tobias MoehlmannHarald Steiner
Feb 4, 2003·Proceedings of the National Academy of Sciences of the United States of America·Meir H ScheinfeldLuciano D'Adamio

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Citations

Feb 3, 2012·Amyloid : the International Journal of Experimental and Clinical Investigation : the Official Journal of the International Society of Amyloidosis·Kazuko MachidaShu-Ichi Ikeda
Feb 13, 2015·Proceedings of the National Academy of Sciences of the United States of America·Jinko SawashitaKeiichi Higuchi
Sep 10, 2008·Neurobiology of Disease·Christopher D LinkGretchen H Stein
May 18, 2016·Organic & Biomolecular Chemistry·Chao ZuoJi-Shen Zheng
Dec 14, 2006·Genetika·A P GalkinS G Inge-Vechtomov
Sep 18, 2007·Analytical Biochemistry·Louis J SparveroChristina M Coughlan
Jul 15, 2009·Biochimica Et Biophysica Acta·Jinko SawashitaKeiichi Higuchi

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