Processing of beta-amyloid precursor protein by cathepsin D.

The Journal of Biological Chemistry
J HigakiB Cordell

Abstract

The events leading to the formation of beta-amyloid (betaA4) from its precursor (betaAPP) involve proteolytic cleavages that produce the amino and carboxyl termini of betaA4. The enzyme activities responsible for these cleavages have been termed beta- and gamma-secretase, respectively, although these protease(s) have not been identified. Since betaA4 is known to possess heterogeneity at both the amino and carboxyl termini, beta- and gamma-secretases may actually be a collection of proteolytic activities or perhaps a single proteolytic enzyme with broad amino acid specificity. We investigated the role of cathepsin D in the processing of betaAPP since this enzyme has been widely proposed as a gamma-secretase candidate. Treatment of a synthetic peptide that spans the gamma-secretase site of betaAPP with human cathepsin D resulted in the cleavage of this substrate at Ala42-Thr43. A sensitive liquid chromatography/mass spectrometry technique was also developed to further investigate the ability of cathepsin D to process longer recombinant betaAPP substrates (156 and 100 amino acids of betaAPP carboxyl terminus) in vitro. The precise cathepsin D cleavage sites within these recombinant betaAPP substrates were identified using this tec...Continue Reading

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Citations

Mar 22, 2013·Molecular Neurobiology·Santosh JadhavMichal Novak
Dec 22, 1999·The International Journal of Biochemistry & Cell Biology·G SadikT Shinoda
Nov 15, 2011·Journal of Clinical Microbiology·Wendy E KamanFloris J Bikker
Dec 11, 2013·Acta Biochimica Et Biophysica Sinica·Lin Qi, Xing-Ding Zhang
Mar 30, 2016·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Genevieve Evin
Jan 10, 2002·The Journal of Biological Chemistry·Francois AuthierGilbert Briand
Jul 5, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jessica B FlechtnerSofija Andjelic
Feb 16, 2017·Cellular and Molecular Life Sciences : CMLS·Leah ZuroffMaya Koronyo-Hamaoui
Apr 8, 2019·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Mohammad A RahmanSantosh Kumar
Nov 5, 2019·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Elisabeth S ButzSusan L Cotman
Oct 20, 2006·Neurobiology of Aging·Lorena UrbanelliAldo Orlacchio

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