Fig. 9

The dysfunction of circRIMS2/miR-3968/UBE2K/GluN2B results in synaptic and memory impairments in AD mice. Under normal condition (left), miR-3968 inhibits UBE2K, and the protein level of GluN2B is maintained. However, in AD (right), Aβ induces an elevation in METTL3, which enhances the stability of circRIMS2 through m6A modification. Consequently, increased circRIMS2 binds competitively with miR-3968, leading to the overexpression of UBE2K. UBE2K interacts with GluN2B, mediating its ubiquitination, degradation, and synaptic dysfunction. The partial rescue of these abnormalities could be achieved by blocking the ubiquitination of K1082 on GluN2B using sip-1082 peptide