Research Perspective Volume 3, Issue 8 pp 803—812

Phosphorylation of amyloid beta (Aβ) peptides – A trigger for formation of toxic aggregates in Alzheimer's disease


Figure 1. Schematic representation of generation of Aβ by proteolytic processing of APP and the familial AD causing APP mutations. (A) Two pathways (β/γ and α/γ) of APP proteolysis. APP can be cleaved by either β- or α-secretase, which is then followed by γ-secretase cleavage results in the generation of either the p3-fragment (non-amyloidogenic) or an Aβ (amyloigenic pathway). The designation of secretases, substrates and products are depicted, (B) Representation of APP familial AD causing mutations that are identified around N- and C-terminal and in the middle region of Aβ. The amino acid residues are numbered according to Aβ sequence. The swedish mutation (KM>NL) at N-terminus of Aβ̣ near to β-secretase cleavage site increases the total production of Aβ, whereas the mutations C-terminus of Aβ results in increased production of Aβ42 by altering γ-secretase activity. The mutations in the middle region of Aβ might decrease the α-secretory cleavage, facilitate the amyloidogenic processing, promote the Aβ production and/or increases the propensity of Aβ aggregation or stabilizes the Aβ against clearance by different proteases.