Description

• Tytuł:
  Interplay between Copper, Neprilysin, and N-Truncation of β-Amyloid
• Twórca:
  Mital, Mariusz;
  Bal, Wojciech;
  Frączyk, Tomasz;
  Drew, Simon
• Opis:
  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.
• Dostępność obiektu:
  free access
• Data:
  2018.06.04
• Typ:
  Article;
  PeerReviewed
• Wydawca:
  ACS Publications
• Relacja: http://eprints.ibb.waw.pl/1656 ;https://pubs.acs.org/doi/10.1021/acs.inorgchem.8b00391
• Temat i słowa kluczowe:
  QD Chemistry;
  QH301 Biology
• Identyfikator:
  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
• Dostawca danych:
  Repozytorium Instytutu Biochemii i Biofizyki Polskiej Akademii Nauk
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