PMID- 30144539
OWN - NLM
STAT- MEDLINE
DCOM- 20190307
LR  - 20190307
IS  - 1872-7972 (Electronic)
IS  - 0304-3940 (Linking)
VI  - 686
DP  - 2018 Nov 1
TI  - Neprilysin degrades murine Amyloid-beta (Abeta) more efficiently than human
      Abeta: Further implication for species-specific amyloid accumulation.
PG  - 74-79
LID - S0304-3940(18)30574-3 [pii]
LID - 10.1016/j.neulet.2018.08.028 [doi]
AB  - For over a century, aggregated forms of amyloid-beta protein (Abeta) have been
      viewed as a key hallmark of brains affected by Alzheimer's disease (AD). Today,
      it remains unknown whether Abeta aggregates (oligomers, fibrils or plaques)
      originate from increased production or decreased catabolism of Abeta. Neprilysin 
      (NEP, neutral endopeptidase) is a ubiquitously distributed peptidase, known to
      degrade Abeta, amongst other peptides. In this study, we identified differences
      in NEP-mediated catabolism of murine and human forms of Abeta, using recombinant 
      human NEP, membrane-bound NEP from cells overexpressing the murine peptidase or
      from human organ preparations with high NEP activity, and purified soluble bovine
      NEP. NEP degraded murine Abeta (mAbeta) faster than human Abeta (hAbeta). These
      findings were observed with full-length Abeta containing 40 or 42 amino acids
      (Abeta1-40 and Abeta1-42) and a truncated form (Abeta4-15), which (i) contains
      one of the main NEP cleavage sites for Abeta (between positions 9 and 10), (ii)
      harbours all three amino acid differences between murine and human Abeta
      sequences, and (iii) is less prone to aggregation and thus might be a simpler
      model to investigate Abeta biochemistry. While it has previously been shown that 
      mAbeta has a far lower propensity to aggregate than hAbeta, evidence from this
      study suggests that a faster NEP-mediated turnover of mAbeta may provide
      additional protection against Abeta aggregation in murine species.
CI  - Copyright (c) 2018. Published by Elsevier B.V.
FAU - Becker, Matthias
AU  - Becker M
AD  - Leibnizinstitut fur Molekulare Pharmakologie (FMP), Berlin, Germany.
FAU - Moore, Andrew
AU  - Moore A
AD  - Department of Pharmacology and Therapeutics, School of Medicine and School of
      Pharmacy, University College Cork, Cork, Ireland.
FAU - Naughton, Maura
AU  - Naughton M
AD  - Department of Pharmacology and Therapeutics, School of Medicine and School of
      Pharmacy, University College Cork, Cork, Ireland.
FAU - Boland, Barry
AU  - Boland B
AD  - Department of Pharmacology and Therapeutics, School of Medicine and School of
      Pharmacy, University College Cork, Cork, Ireland.
FAU - Siems, Wolf-Eberhard
AU  - Siems WE
AD  - Leibnizinstitut fur Molekulare Pharmakologie (FMP), Berlin, Germany.
FAU - Walther, Thomas
AU  - Walther T
AD  - Department of Pharmacology and Therapeutics, School of Medicine and School of
      Pharmacy, University College Cork, Cork, Ireland; Institute of Medical
      Biochemistry and Molecular Biology, University Medicine Greifswald, Greifswald,
      Germany. Electronic address: t.walther@ucc.ie.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180823
PL  - Ireland
TA  - Neurosci Lett
JT  - Neuroscience letters
JID - 7600130
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Peptide Fragments)
RN  - EC 3.4.24.11 (Neprilysin)
SB  - IM
MH  - Alzheimer Disease/metabolism
MH  - Amyloid beta-Peptides/*metabolism
MH  - Brain/*metabolism
MH  - Humans
MH  - Neprilysin/*metabolism
MH  - Neurons/*metabolism
MH  - Peptide Fragments/metabolism
MH  - Species Specificity
OTO - NOTNLM
OT  - *Alzheimer's disease
OT  - *Amyloid-beta protein
OT  - *Abeta
OT  - *Catabolism
OT  - *Neprilysin
OT  - *Neuroscience
OT  - *Neutral endopeptidase
EDAT- 2018/08/26 06:00
MHDA- 2019/03/08 06:00
CRDT- 2018/08/26 06:00
PHST- 2016/11/29 00:00 [received]
PHST- 2018/08/14 00:00 [revised]
PHST- 2018/08/21 00:00 [accepted]
PHST- 2018/08/26 06:00 [pubmed]
PHST- 2019/03/08 06:00 [medline]
PHST- 2018/08/26 06:00 [entrez]
AID - S0304-3940(18)30574-3 [pii]
AID - 10.1016/j.neulet.2018.08.028 [doi]
PST - ppublish
SO  - Neurosci Lett. 2018 Nov 1;686:74-79. doi: 10.1016/j.neulet.2018.08.028. Epub 2018
      Aug 23.