Title |
Neprilysin degrades murine Amyloid-β (Aβ) more efficiently than human Aβ: Further implication for species-specific amyloid accumulation
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Published in |
Neuroscience Letters, August 2018
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DOI | 10.1016/j.neulet.2018.08.028 |
Pubmed ID | |
Authors |
Matthias Becker, Andrew Moore, Maura Naughton, Barry Boland, Wolf-Eberhard Siems, Thomas Walther |
Abstract |
For over a century, aggregated forms of amyloid-β protein (Aβ) have been viewed as a key hallmark of brains affected by Alzheimer's disease (AD). Today, it remains unknown whether Aβ aggregates (oligomers, fibrils or plaques) originate from increased production or decreased catabolism of Aβ. Neprilysin (NEP, neutral endopeptidase) is a ubiquitously distributed peptidase, known to degrade Aβ, amongst other peptides. In this study, we identified differences in NEP-mediated catabolism of murine and human forms of Aβ, 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 Aβ (mAβ) faster than human Aβ (hAβ). These findings were observed with full-length Aβ containing 40 or 42 amino acids (Aβ1-40 and Aβ1-42) and a truncated form (Aβ4-15), which (i) contains one of the main NEP cleavage sites for Aβ (between positions 9 and 10), (ii) harbours all three amino acid differences between murine and human Aβ sequences, and (iii) is less prone to aggregation and thus might be a simpler model to investigate Aβ biochemistry. While it has previously been shown that mAβ has a far lower propensity to aggregate than hAβ, evidence from this study suggests that a faster NEP-mediated turnover of mAβ may provide additional protection against Aβ aggregation in murine species. |
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