Figure 4.

Proposed involvement of G-quadruplexes in Alzheimer's disease. Through the differential cleavage of APP, G4s participate in the regulation of Aβ biogenesis, either by affecting either the expression of APP itself or that of APP-processing enzymes. A G4 motif in the 3′-UTR of APP mRNA has been found to negatively regulate APP translation. A G4 motif within the coding region of BACE1 mRNA may act as a recruitment site for splice regulator hnRNP H, resulting in favored production of the full-length BACE1 501 transcript isoform and leading to enhanced APP proteolysis and Aβ production. Also, a G4 motif within the 5′-UTR of ADAM10 mRNA negatively regulates the production of ADAM10 α-secretase activity, thereby suppressing cleavage of APP and contributing to Aβ production.