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Drosophila Neprilysin 1 Rescues Memory Deficits Caused by Amyloid-β Peptide.

Authors :
Turrel, Oriane
Goguel, Valerie
Preat, Thomas
Source :
Journal of Neuroscience. 10/25/2017, Vol. 37 Issue 43, p10334-10345. 12p.
Publication Year :
2017

Abstract

Neprilysins are Type II metalloproteinases known to degrade and inactivate a number of small peptides, in particular the mammalian amyloid-β peptide (Aβ). In Drosophila, several neprilysins expressed in the brain are required for middle-term (MTM) and long-term memory (LTM) in the dorsal paired medial (DPM) neurons, a pair of large neurons that broadly innervate the mushroom bodies (MB), the center of olfactory memory. These data indicate that one or several peptides need to be degraded for MTM and LTM. We have previously shown that the fly amyloid precursor protein (APPL) is required for memory in the MB. We show here that APPL is also required in adult DPM neurons for MTM and LTM formation. This finding prompted us to search for an interaction between neprilysins and Drosophila Aβ (dAβ), a cleavage product of APPL. To find out whether dAβ was a neprilysin's target, we used inducible drivers to modulate neprilysin 1 (Nep1) and dAβ expression in adult DPM neurons. Experiments were conducted either in both sexes or in females. We show that Nep1 inhibition makes dAβ expression detrimental to both MTM and LTM. Conversely, memory deficits displayed by dAβ-expressing flies are rescued by Nep1 overexpression. Consistent with behavioral data, biochemical analyses confirmed that Nep1 degrades dAβ. Together, our findings establish that Nep1 and dAβ expressed in DPM neurons are functionally linked for memory processes, suggesting that dAβ is a physiological target for Nep1. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
02706474
Volume :
37
Issue :
43
Database :
Academic Search Index
Journal :
Journal of Neuroscience
Publication Type :
Academic Journal
Accession number :
126101298
Full Text :
https://doi.org/10.1523/JNEUROSCI.1634-17.2017