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

Figure 1

Proteolytic processing of amyloid precursor protein. In the nonamyloidogenic pathway, transmembrane APP is cleaved by α-secretase followed by γ-secretase generating a nontoxic P3 fragment and α C-terminal fragments (α-CTFs), thus preventing the generation of toxic Aβ. Alternatively, the amyloidogenic pathway involves sequential cleavages of APP by β-secretase followed by γ-secretase complex, thus generating toxic Aβ peptides in addition to the β-CTFs and amyloid precursor protein intracellular domain (AICD). The accumulation of Aβ peptides promotes oligomerisation and formation of insoluble plaques.