Several neurodegenerative diseases are associated with defects in the gene encoding membrane metalloendopeptidase (MME, MIM:120520); this membrane-bound endopeptidase cleaves a number of different peptide hormones. See links in 'Related Diseases' for information on specific diseases associated with MME. There are multiple related genes in both human and Drosophila; the fly Nep1, Nep4 and Nep2 genes are most closely related to MME; RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated for these three genes. Nep1, Nep4 and Nep2 are also closely related to the human genes MMEL1 and PHEX.
A UAS construct of the wild-type human Hsap\MME has been introduced into flies. Neuronal overexpression of Hsap\MME results in age-dependent axon degeneration and a shortened lifespan.
Overexpression of Nep2 has been shown to reduce neurodegeneration phenotypes observed in a Drosophila model using human Hsap\APP-derived amyloid beta peptides (FBrf0179205, FBrf0205107); significantly lower levels of amyloid beta peptides are observed. Overexpression of Nep1 rescues memory defects observed in a similar model using Dmel\Appl-derived amyloid beta peptides (FBrf0237026).
[updated Jul. 2019 by FlyBase; FBrf0222196]
MME (membrane metalloendopeptidase) encodes a membrane-bound endopeptidase that cleaves peptides at the amino side of hydrophobic residues; it inactivates a number of peptide hormones including glucagon, enkephalins, substance P, neurotensin, angiotensin, oxytocin, bradykinin, and atrial natriuretic factor. [from Gene Cards, MME; 2017.09.25]
Many to many: multiple related genes in both species.
High-scoring ortholog of human MME and MMEL1 (many Drosophila to many human). Dmel\Nep1 shares 40-41% identity and 58-59% similarity with the human genes.
Moderate-scoring ortholog of human MME, MMEL1 and PHEX (many Drosophila to many human). Dmel\Nep2 shares 34-38% identity and 54-56% similarity with the human genes.
