Astrocytes are a functionally diverse cell population that exerts a complex range of effects on neurons in the central nervous system (CNS). These include actions both supportive to neuron homeostasis (i.e., release of lactate and promotion of post-traumatic tissue repair) as well as destructive (i.e., driving CNS inflammation and neurodegeneration). These negative processes can involve multiple mechanisms including neurotoxicity, modulation of microglial responses, and recruitment of inflammatory cells. Using a combination of proteomic, metabolomic, transcriptomic, and perturbation approaches, Dr. Chun-Cheih Chao found that sphingolipid metabolism in astrocytes trigger the interaction of cytosolic phospholipase A2 (cPLA2) with mitochondrial antiviral signaling protein (MAVS). This stimulates NF-κB-driven transcriptional programs leading to CNS inflammation and disruption of MAVS-hexokinase 2 (HK2) interactions that result in decreased lactate production and compromised neuronal metabolism. Dr. Chao will describe how this sequence of events can be pharmacologically targeted to treat neuroinflammation.
Identifying PIK3CA variants provides a reliable tool for screening clinically relevant mutations in breast cancer tumors. Leading experts, Dr. Werner Schroth and the Dr. Alexander... Continue reading