Neurosciences
Cell Signaling & Apoptosis
Joan X. Comella Carnicé
Researchers Joaquín López Soriano, Bruna Barneda Zahonero, Nuria Llecha Cano, Laura Planells Ferrer, Jorge Urresti Ibáñez, Koen Galenkamp | Researchers in training Elena Coccia, Isabel Calleja Yagüe, Blanca Sanuy Escribano
Summary
Our main goal is to characterize the role of two death receptor antagonists, FAIM-L and Lifeguard, in nervous system physiology.
We characterized Lifeguard subcellular localization, showing that is most present in Golgi and reticulum. Its protection on FasL-induced cell death on neuroblastoma cell lines is dependent on calcium release inhibition at the reticulum, thus showing a previously undescribed molecular mechanism of action for this protein.
We studied the role of FAIM-L in neurons in Alzheimer‘s disease patients and animal models of the disease (mice APP/PS1). FAIM-L levels are downregulated both in AD patients and mice brains. Mice neurons in vitro cultivated with amyloid beta showed reduced FAIM-L levels. The protection afforded by TNF as a pro-inflammatory signal against amyloid beta toxicity is lost when FAIM-L levels decrease. Thus, FAIM-L can contribute to determine the protective or deleterious effects of TNF in neurons in a neuroinflammatory context.