Targeting WNT, protein kinase B, and mitochondrial membrane integrity to foster cellular survival in the nervous system

摘要: Summary Targeting essential cellular pathways that determine neuronal and vascular survival can foster a successful therapeutic platform for the treatment of wide variety degenerative disorders in central nervous system. In particular, oxidative injury precipitate several system may either be acute nature, such as during cerebral ischemia, or more progressive chronic, Alzheimer disease. Apoptotic brain proceeds through two distinct ultimately result early externalization membrane phosphatidylserine (PS) residues late induction genomic DNA fragmentation. Degradation acutely impact survival, while exposure PS lead to microglial phagocytosis viable cells, inflammation, thrombosis Through independent common pathways, Wingless/Wnt pathway serine-threonine kinase Akt serve roles maintenance integrity prevention phagocytic disposal cells "tagged" by exposure. By selectively governing activity specific downstream substrates include GSK-3β, Bad, β-catenin, Wnt block programmed cell death. Novel is its capacity protect from direct modulation Intimately linked activation signaling mitochondrial potential regulation Bcl-xL, energy metabolism, cytochrome c release cysteine protease activation.