©2005 by MEDIMOND S.r.l. 25 F517R9034 Cyclooxygenases and Prostaglandin E 2 in Animal and Human Prion Diseases L. Minghetti, M. Sbriccoli, M.C. Geloso, L. Ingrosso, M.A. Di Bari, A. Greco, F. Cardone and M. Pocchiari Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy Summary The strong induction of cyclooxygenase-2 (COX-2) expression in experimental prion diseases suggests its involvement in the pathogenesis of these neurodegenerative diseases. The increased COX expression and prostaglandin E 2 (PGE 2 ) synthesis in animal models are consistent with the elevated levels PGE 2 in the cerebro-spinal fluid of subjects affected by genetic or sporadic Creutzfeldt-Jakob disease (CJD) or by variant CJD, the novel human form associated with the consumption of contaminated bovine products. In sporadic CJD patients, higher CSF levels of PGE 2 were associated with shorter survival. Whether PGE 2 contributes to neurodegeneration in CJD or is associated with apoptotic neuron clearance and/or prion protein accumulation is still unknown. Introduction Prion diseases or transmissible spongiform encephalopathies are a heterogeneous group of infectious, sporadic and genetic disorders. Creutzfeldt-Jakob disease is the most known human form of transmis- sible spongiform encephalopathies and is characterized by rapidly pro- gressive dementia and by more than 90% mortality within one year from the onset. The characteristic neuropathological signs of the disease are amyloid deposition of the pathological prion protein (PrP TSE ), astrocytosis and spongiform degeneration. A further disease hallmark is the exten- sive microglial activation, which is believed to sustain a local non- immune mediated chronic inflammatory response. Cyclooxygenase (COX), catalyses the first committed step in the