Cytoskeleton-Associated Risk Modifiers Involved in Early and Rapid Progression of Sporadic Creutzfeldt-Jakob Disease.

摘要: A high priority in the prion field is to identify pre-symptomatic events and associated profile of molecular changes. In this study, we demonstrate dysregulation cytoskeleton assembly its cofilin-1 pathway strain brain region-specific manners MM1 VV2 subtype-specific Creutzfeldt-Jakob disease at clinical pre-clinical stage. At physiological level, PrPC interaction with phosphorylated form cofilin (p-cofilin(Ser3)) was investigated primary cultures mouse cortex neurons (PCNs) wild-type knockout mice (PrP-/-). Short-interfering RNA downregulation active resulted redistribution/downregulation PrPC, increase activated microglia, accumulation dense F-actin, upregulation p-cofilin(Ser3). This upregulated p-cofilin(Ser3) showed redistribution expression predominantly microglia PCNs. pathological significantly altered cerebellum both humans stage early symptomatic disease. Further, better understand possible mechanism cofilin-1, also demonstrated alterations upstream regulators; LIM kinase isoform 1 (LIMK1), slingshot phosphatase (SSH1), RhoA-associated (Rock2), amyloid precursor protein (APP) sporadic human frontal samples. conclusion, our findings for first time a key response