Evidence Details for Wwp2
PMID Title Journal Year Abstract
37066940 Acupuncture improves learning and memory ability of posttraumatic stress disorder model rats through epigenetic regulation of microglial phosphatidylinositol 3-kinase pathway. Technol Health Care. 2023;31(S1):409-421. doi: 10.3233/THC-236035. 2023 BACKGROUND: Microglia express phosphatidylinositol 3-kinase (PI3K) has been implicated in the induction and maintenance of long-term potentiation (LTP) and in hippocampal synaptic plasticity. However, there are few studies on the interference of PI3K signal pathway in microglia. OBJECTIVE: The study goal is to gain a better understanding of the mechanism by which EA affects synapses provides insights into how electroacupuncture (EA) modulates synaptic plasticity in learning and memory. METHODS: Rat models of posttraumatic stress disorder (PTSD) were used to explore the effects of EA on microglial PI3K pathway, brain-derived neurotrophic factor (BDNF) and LTP, and the target and mechanism underlying the effects of EA on PI3K from the perspective of protein ubiquitination. RESULTS: EA induced microglial BDNF expression by activating the PI3K-AKT pathway, thereby facilitating LTP and synaptic plasticity. EA inhibited lincRNA 02023 to rescue the binding of WWP2 to PTEN, thereby promoting PTEN ubiquitination and degradation. CONCLUSION: The mechanism of EA improving the learning and memory ability of PTSD rats may be that it can promote the competitive combination of WWP2 and PTEN by inhibiting Linc RNA02023, and then lead to microglial PI3K and its pathway activation, BDNF up-regulation, and finally induce LTP and repair damaged synaptic plasticity."

Evidence Sentence: EA inhibited lincRNA 02023 to rescue the binding of WWP2 to PTEN, thereby promoting PTEN ubiquitination and degradation.
Evidence Sentence: The mechanism of EA improving the learning and memory ability of PTSD rats may be that it can promote the competitive combination of WWP2 and PTEN by inhibiting Linc RNA02023, and then lead to microglial PI3K and its pathway activation, BDNF up-regulation, and finally induce LTP and repair damaged synaptic plasticity.
Evidence Sentence: PI3K activation due to lincRNA 02023 interference of WWP2 binding to PTEN
Evidence Sentence: The domain of the PTEN protein (amino acids 101-179) is considered the main RNA binding region; this region is also the binding site for the E3 ubiquitin ligase WWP2 (amino acids 100-187); that is, the binding sites of PTEN for lincRNA 02023 and WWP2 overlap.
Evidence Sentence: More importantly, we investigated the effect of lincRNA 02023 overexpression on the binding of WWP2 to PTEN.
Evidence Sentence: 4B, both the lincRNA 02023 overexpression (lincRNA 02023) group and the SPS group exhibited decreased ubiquitination of PTEN and decreased binding between PTEN and WWP2; these decreases rescued the expression of PI3K and AKT ( 0.01, Fig.
Evidence Sentence: We further verified that EA influenced the binding of WWP2 to PTEN.
Evidence Sentence: 4B, compared with the SPS group, both the lincRNA 02023EA and EA groups exhibited greater ubiquitination of PTEN and increased protein expression of PTEN, ultimately enhancing the binding affinity of PTEN for WWP2.
Evidence Sentence: These results suggest that EA increases the ubiquitination of PTEN (and thus promotes its degradation) by inhibiting the expression of lincRNA 02023; the lack of competition of lincRNA 02023 at the binding site of PTEN promotes the binding of WWP2 to PTEN, thereby upregulating the expression of PI3K and AKT ( 0.01, Fig.
Evidence Sentence: In the present study, we found that the expression of lincRNA 02023 was abnormally upregulated, weakening the ability of WWP2 to bind to PTEN.
Evidence Sentence: Further investigation indicated that EA inhibited lincRNA 02023 and thus rescued the binding of WWP2 to PTEN, promoting PTEN ubiquitination and degradation to activate the PI3K-AKT pathway, which is a key factor in regulating LTP and restoring synaptic plasticity.