“…Like APP, APPL is subject to proteolytic processing by α, β, and γ-secretases that generate an analogous spectrum of cleavage fragments, including sAPPs, CTFs, AICDs, and an Aβ-like peptide (Luo et al, 1995; Greeve et al, 2004; Carmine-Simmen et al, 2009; Poeck et al, 2012). Also like mammalian APP, APPL plays important roles in the developing nervous system, participating in the control of neuronal migration and synaptic plasticity (Torroja et al, 1999; Ashley et al, 2005; Ramaker et al, 2013; Soldano et al, 2013; Bourdet et al, 2015). Notably, studies in Drosophila have shown that defects caused by the loss of APPL can be rescued by the expression of human APP 695 (Luo et al, 1992; Wentzell et al, 2012), indicating that these proteins are both structurally and functionally homologous.…”