Exp Neurol. 2006 Dec;202(2):410-20. Epub 2006 Aug 17.

Evidence of tumor necrosis factor receptor 1 signaling in human temporal lobe epilepsy.External

Yamamoto, A., Schindler, C. K., Murphy, B. M., Bellver-Estelles, C., So, N. K., Taki, W., Meller, R., Simon, R. P., Henshall, D. C.,
--- - Robert S. Dow Neurobiology laboratories, Legacy Research, Portland, OR, USA.
Seizures, particularly when prolonged, may cause neuronal loss within vulnerable brain structures such as the hippocampus, in part by activating programmed (apoptotic) cell death pathways. Experimental modeling suggests that seizures activate tumor necrosis factor receptor 1 (TNFR1) and engage downstream pro- and anti-apoptotic signaling cascades. Whether such TNFR1-mediated signaling occurs in human temporal lobe epilepsy (TLE) is unknown. Presently, we examined this pathway in hippocampus surgically obtained from refractory TLE patients and contrasted findings to matched autopsy controls. Western blotting established that total protein levels of the TNFR1 proximal signaling adaptor TNFR-associated protein with death domain (TRADD), cleaved initiator caspase-8 and apoptosis signal-regulating kinase 1 (ASK1) were higher in TLE samples than controls. Intracellular distribution analyses revealed raised cytoplasmic levels of TNFR1, TRADD and the caspase-8 recruitment adaptor Fas-associated protein with death domain (FADD), and higher levels of TRADD and cleaved caspase-8 in the microsomal fraction, in TLE samples. Immunoprecipitation studies detected TRADD-FADD binding, and fluorescence microscopy revealed TRADD co-localization with FADD in TLE hippocampus. These data suggest that TNFR1 signaling is engaged in the hippocampus of patients with refractory temporal lobe epilepsy.
PMID: 16919273External
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vivo interaction
  Endogenous
expression
Overexpression DD1 DD2 Reference
Family DD1 DD2 Method Species Region Species Region
DD FADD Link TRADD Co-Immunofluorescence staining Human TLE hammacampus section 16919273
DD FADD Link TRADD Co-immunoprecipitation Human TLE hammacampus lysate 16919273
DD TNFR1 Link TRADD Co-immunoprecipitation Human TLE hammacampus lysate 16919273
(Link: click this icon to show interactions only between the two corresponding DDs)