Figure 2.
Therapeutic development strategies for AD (The ‘PrPC axis’). The green color portion of PrPC indicates the protective function of PrPC (left-hand side), and the red color portion of PrPC indicates PrPC as the receptor of Aβ oligomers (righthand side) to mediate the Aβ toxicity. The left-hand side of the figure indicates therapeutic strategies by enhancing the normal function of PrPC (enhancing the inhibitory effect on BACE1, which reduces Aβ production, and enhancing the α-cleavage, which increases production of the protective N1 fragment of PrPC). The right-hand side of the figure indicates therapeutic strategies by targeting the Aβ oligomer/PrPC-mediated toxic signaling pathway, which encompass measures to inhibit Aβ oligomerization, Aβ prion-like activity, interaction of Aβ oligomers with PrPC, Aβ oligomer/PrPC-mediated disinhibition of BACE1, intermediate mediators (such as caveolin-1 and NCAM), Fyn kinase, and prion-like activity of hyperphosphorylated Tau. (Abbreviations: Aβo: Aβ oligomers; N1: N1 fragment of PrPC; p-Tau: hyperphosphorylated Tau.)