| First Author | Mir S | Year | 2014 |
| Journal | Mol Cell | Volume | 56 |
| Issue | 6 | Pages | 786-95 |
| PubMed ID | 25435139 | Mgi Jnum | J:218792 |
| Mgi Id | MGI:5618391 | Doi | 10.1016/j.molcel.2014.10.019 |
| Citation | Mir S, et al. (2014) Cytokine-induced GAPDH sulfhydration affects PSD95 degradation and memory. Mol Cell 56(6):786-95 |
| abstractText | Induction of a proinflammatory cytokine, interleukin-1beta (IL-1beta) plays a role in memory impairment associated with various neurological disorders and brain injury. Here we show that IL-1beta-induced memory impairment in brain is mediated by hydrogen sulfide (H2S) synthesized by cystathionine beta-synthase (CBS). H2S modifies GAPDH essentially via sulfhydration in dendrites, which promotes its binding to the E3 ligase protein, Siah. Then Siah binds to a critical synaptic scaffolding molecule, PSD95, and leads it to degradation via ubiquitination. In CBS heterozygous mice (cbs(+/-)) and primary neurons depleted with either CBS or IL-1R, IL-1beta-induced loss of PSD95 was rescued along with a decrease in the level of GAPDH sulfhydration. Moreover, decrease in the loss of PSD95 in cbs(+/-) mice results in improvement of IL-1beta-induced cognitive deficits and neurobehavioral outcomes. Thus, our findings reveal a mechanism where GAPDH sulfhydration appears to be a physiologic determinant of cytokine-induced memory impairment in brain. |
