Review Article

Using Drosophila Models of Amyloid Toxicity to Study Autophagy in the Pathogenesis of Alzheimer’s Disease

Table 2

The human genes that function in APP proteolysis and their Drosophila orthologues.

Human geneDrosophila geneFunctions

Amyloid precursor protein (APP)ApplAPP is an integral membrane protein containing an Aβ-like region that is cleaved by BACE1.
Amyloid precursor-like proteins (APLP1 and APLP2)Sequence divergence at the internal Aβ site of APLP1 and APLP2 prevents cleavage by BACE1. The principal functions of APLP1 and APLP2 remain unknown.

Presenilin 1PresenilinThe catalytic subunit of the γ-secretase enzyme complex, also required for lysosomal acidification.
Presenilin 2Component of γ-secretase complex.

ADAM 10KuzbanianA neuronal α-secretase that cleaves APP at the plasma membrane via nonamyloidogenic processing.

BACE1Baceβ-secretase enzyme activity cleaves APP in early endosome and promotes amyloidogenic processing with Aβ production.
BACE2β-secretase related to BACE1 that is thought to contribute to Alzheimer’s disease.