Intracellular domain generation of amyloid precursor protein by ε-cleavage depends on C-terminal fragment by α-secretase cleavage

  • Authors:
    • Hideaki Kume
    • Kei Maruyama
    • Fuyuki Kametani
  • View Affiliations

  • Published online on: January 1, 2004     https://doi.org/10.3892/ijmm.13.1.121
  • Pages: 121-125
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

A significant accumulation of Aβ is major pathological feature in the brain in patients with Alzheimer's disease (AD). Amyloid precursor protein (APP) is cleaved by α- and β-secretase, resulting in secretion of extracellular domain. Then the remaining membrane-anchored C-terminal fragments (CTFα or CTFβ) are cleaved by γ-secretase. Therefore, Aβ is derived from APP by sequential proteolytic processing involving 2 proteases, called β- and γ-secretase. γ-Secretase cleavage results in the generation of the APP intracellular domain (AICD), as well as Aβ. Recently, AICD is generated by ε-cleavage site near the cytoplasmic membrane boundary of APP, not by γ-cleavage site in the middle of transmembrane domain. We show that elevated β-secretase levels induced the increase in CTFβ and Aβ generation and reduction of CTFα and AICD generation in vitro. Furthermore, elevated α-secretase levels induced an increase of AICD. The results suggest that generation of AICD by ε-cleavage depends on CTFα and that γ- and ε-cleavage are differentially regulated.

Related Articles

Journal Cover

January 2004
Volume 13 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Kume H, Maruyama K and Kametani F: Intracellular domain generation of amyloid precursor protein by ε-cleavage depends on C-terminal fragment by α-secretase cleavage. Int J Mol Med 13: 121-125, 2004
APA
Kume, H., Maruyama, K., & Kametani, F. (2004). Intracellular domain generation of amyloid precursor protein by ε-cleavage depends on C-terminal fragment by α-secretase cleavage. International Journal of Molecular Medicine, 13, 121-125. https://doi.org/10.3892/ijmm.13.1.121
MLA
Kume, H., Maruyama, K., Kametani, F."Intracellular domain generation of amyloid precursor protein by ε-cleavage depends on C-terminal fragment by α-secretase cleavage". International Journal of Molecular Medicine 13.1 (2004): 121-125.
Chicago
Kume, H., Maruyama, K., Kametani, F."Intracellular domain generation of amyloid precursor protein by ε-cleavage depends on C-terminal fragment by α-secretase cleavage". International Journal of Molecular Medicine 13, no. 1 (2004): 121-125. https://doi.org/10.3892/ijmm.13.1.121