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Journal article
Cathepsin L Mediates the Degradation of Novel APP C-Terminal Fragments
Biochemistry (Easton), v 54(18), pp 2806-2816
12 May 2015
PMID: 25910068
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Alzheimer's disease (AD) is characterized by the deposition of amyloid β (Aβ), a peptide generated from proteolytic processing of its precursor, amyloid precursor protein (APP). Canonical APP proteolysis occurs via α-, β-, and γ-secretases. APP is also actively degraded by protein degradation systems. By pharmacologically inhibiting protein degradation with ALLN, we observed an accumulation of several novel APP C-terminal fragments (CTFs). The two major novel CTFs migrated around 15 and 25 kDa and can be observed across multiple cell types. The process was independent of cytotoxicity or protein synthesis. We further determine that the accumulation of the novel CTFs is not mediated by proteasome or calpain inhibition, but by cathepsin L inhibition. Moreover, these novel CTFs are not generated by an increased amount of BACE. Here, we name the CTF of 25 kDa as η-CTF (eta-CTF). Our data suggest that under physiological conditions, a subset of APP undergoes alternative processing and the intermediate products, the 15 kDa CTFs, and the η-CTFs aret rapidly degraded and/or processed via the protein degradation machinery, specifically, cathepsin L.
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Details
- Title
- Cathepsin L Mediates the Degradation of Novel APP C-Terminal Fragments
- Creators
- Haizhi Wang - Drexel UniversityNianli Sang - Drexel UniversityCan Zhang - Massachusetts General HospitalRamesh Raghupathi - Drexel UniversityRudolph E Tanzi - Massachusetts General HospitalAleister Saunders - Drexel University
- Publication Details
- Biochemistry (Easton), v 54(18), pp 2806-2816
- Publisher
- American Chemical Society; Washington, DC
- Grant note
- P30 AG062421 / NIA NIH HHS R01 CA129494 / NCI NIH HHS P50 AG005134 / NIA NIH HHS R01 NS057295 / NINDS NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology; Neurobiology and Anatomy
- Web of Science ID
- WOS:000354578800003
- Scopus ID
- 2-s2.0-84929148822
- Other Identifier
- 991019167994504721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology