. Catabolic attacks of membrane-bound angiotensin-converting enzyme on the N-terminal part of species-specific amyloid-beta peptides. Eur J Pharmacol. 2008 Jun 24;588(1):18-25. PubMed.

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  1. This study is a comprehensive investigation into the behavior of both catalytic sites of angiotensin converting enzyme (ACE)-mediated cleavage of Aβ peptide. It also investigates whether there are species differences between how human or mouse (ACE) interact with and degrade human or mouse Aβ. These latter questions formed the basis of very valuable dialogue (see comments) that arose previously in Alzforum between Matthew Hemming and myself and Seth Love in response to a prior paper by Chris Eckman and colleagues (Eckman et al., 2006).

    With a number of in vitro and animal studies now published in this area, some of which argue in favor and others against implications for Aβ-related pathology with respect to ACE and its inhibition, this paper by Sun et al. fills a previous void in this growing area of interest. Namely, following some of the previous in vivo studies, there has been debate on how murine ACE might interact with the human Aβ (and endogenous murine Aβ) in these animals and whether that may relate to some negative results. Similarly, there still also remains a lack of agreement on the point of cleavage in Aβ by ACE from in vitro studies. This study comprehensively addresses both of these areas and in addition investigates the basis of interaction between human ACE and either human or murine Aβ, which may still be investigated in animals transgenic for both ACE and APP. In short, the study of Sun et al. will provide some additional help in the interpretation of what currently remain some complicated results with respect to studies of ACE mediated degradation of Aβ.

    References:

    . Regulation of steady-state beta-amyloid levels in the brain by neprilysin and endothelin-converting enzyme but not angiotensin-converting enzyme. J Biol Chem. 2006 Oct 13;281(41):30471-8. PubMed.