Fig. 7

A peptide blocking UBE2K/GluN2B ubiquitination rescues synaptic and memory impairments in APP/PS1 mice. a N2a cells were transfected with UBE2K for 12 h, followed by treatment with sip-1082 or sip-1097 at 1 μM or 10 μM for an additional 24 h, as indicated. The protein levels of GluN2B and UBE2K were tested by WB (n = 4). b Upper part: A schematic diagram of the experiment is presented. The sip-1082 or scramble peptide (15 mg/kg per day) was injected intraperitoneally in 12-month-old APP/PS1 mice for a period of 2 weeks. Then, the mice underwent NOR and MWM, as well as WB and Golgi staining. Lower part: The preference index of the NOR test was calculated. c, d The performance in MWM, including the latencies and the representative traces during the learning stage (c), and the crossings on day 7 (d) (n = 10). e–g Golgi-cox staining was performed to assess the dendritic spines, and representative images are presented (e). Changes of spine density (f) and the percentage of mushroom spines (g) are presented. h–j The representative images of the dendritic trees (h). Scale bar, 50 μm. The Sholl analysis evaluates the distribution of dendritic intersections (i). The DCI analysis assesses the overall complexity of the dendritic arbor (j). k, l Co-Ip (k) and WB (l) to examine the ubiquitination and protein levels of GluN2B in hippocampus of APP/PS1 mice injected with sip-1082 or scramble peptides (n = 3). Data are presented as mean ± SEM and two-tailed t tests were used unless otherwise specified. *P < 0.05, **P < 0.01, ***P < 0.001