LAUSR

The p75 neurotrophin receptor (p75NTR), a member of tumor necrosis factor receptor superfamily, involves in neuronal apoptosis after intracerebral hemorrhage (ICH). It has been previously demonstrated that phosphorylation of p35 is a crucial factor for fighting against the proapoptotic p25/CDK5 signaling in neuronal apoptosis. Then, in ICH models of rats and primary cortical neurons, we found that the expressions of p75NTR, p‐histone H1 (the kinase activity of CDK5), p25, Fas‐associated phosphatase‐1 (FAP‐1), and phosphorylated myocyte enhancer factor 2D (p‐MEF2D) were enhanced after ICH, whereas the expression of p35‐Thr(138) was attenuated. Coimmunoprecipitation analysis indicated several interactions as follows: p35/p25 and CKD5, p75NTR and p35, as well as p75NTR and FAP‐1. After p75NTR or FAP‐1 depletion with double‐stranded RNA interference in PC12 cells, the levels of p25 and p‐histone H1 were attenuated, whereas p35‐Thr(138) was elevated. Considering p75NTR has no effect of dephosphorylation, our results suggested that p75NTR might promote the dephosphorylation of p35‐Thr(138) via interaction with FAP‐1, and the p75NTR/p35 complex upregulated p25/CDK5 signaling to facilitate the neuronal apoptosis following ICH. So, in the study, we aimed to provide a theoretical and experimental basis that p75NTR could be regulated to reduce neuronal apoptosis following ICH for potential clinical treatment.