Amyloidosis in Alzheimer’s Disease: The Toxicity of Amyloid Beta (Aβ), Mechanisms of Its Accumulation and Implications of Medicinal Plants for Therapy

Figure 1

Proteolytic processing of amyloid precursor protein (APP). Amyloid precursor protein (APP) is a ubiquitously expressed integral membrane protein that can be processed in two distinct pathways. In the nonamyloidogenic pathway, APP is cleaved within the Aβ domain by the α-secretase enzyme. However, in the amyloidogenic pathway, APP is first cleaved by β-secretase (BACE1), instead of α-secretase, at the N-terminus of the Aβ domain, and this is followed by γ-secretase cleavage at the C-terminus. This sequence of events generates the Aβ amylogenic peptides, which can aggregate into oligomers and form extracellular neurotoxic plaques in the brain. Both pathways release identical APP intracellular C-terminal domain (AICD). This figure was adapted from Thinakaran and Koo (2008) [11].