IBB PAS Repository

Interplay between Copper, Neprilysin, and N-Truncation of β-Amyloid

Mital, Mariusz and Bal, Wojciech and Frączyk, Tomasz and Drew, Simon (2018) Interplay between Copper, Neprilysin, and N-Truncation of β-Amyloid. Inorganic Chemistry, 57 (11). pp. 6193-6197. ISSN Print Edition ISSN: 0020-1669 Web Edition ISSN: 1520-510X

Full text not available from this repository.

Official URL: https://pubs.acs.org/doi/10.1021/acs.inorgchem.8b0...


Sporadic Alzheimer's disease (AD) is associated with an inefficient clearance of the β-amyloid (Aβ) peptide from the central nervous system. The protein levels and activity of the Zn2+-dependent endopeptidase neprilysin (NEP) inversely correlate with brain Aβ levels during aging and in AD. The present study considered the ability of Cu2+ ions to inhibit human recombinant NEP and the role for NEP in generating N-truncated Aβ fragments with high-affinity Cu2+ binding motifs that can prevent this inhibition. Divalent copper noncompetitively inhibited NEP ( Ki = 1.0 μM), while proteolysis of Aβ yielded the soluble, Aβ4-9 fragment that can bind Cu2+ with femtomolar affinity at pH 7.4. This provides Aβ4-9 with the potential to act as a Cu2+ carrier and to mediate its own production by preventing NEP inhibition. Enzyme inhibition at high Zn2+ concentrations ( Ki = 20 μM) further suggests a mechanism for modulating NEP activity, Aβ4-9 production, and Cu2+ homeostasis.

Item Type:Article
Subjects:Q Science > QD Chemistry
Q Science > QH Natural history > QH301 Biology
Divisions:Department of Biophysics
ID Code:1656
Deposited By: Tomasz Frączyk
Deposited On:07 Dec 2018 08:52
Last Modified:07 Dec 2018 08:52

Repository Staff Only: item control page