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Neurodegenerative diseases can affect abstract thinking, skilled movements, emotional feelings, cognition, memory and other abilities. This diverse group of diseases includes Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), transmissible spongiform encephalopathies (TSE) and amyotrophic lateral sclerosis (ALS). Recent evidence indicates that these diverse neurodegenerative diseases might have a common cause and pathological mechanism—the misfolding, aggregation and accumulation of proteins in the brain, resulting in neuronal apoptosis. Studies from different disciplines strongly support this hypothesis and indicate that a common therapy for these devastating disorders might be possible. We found that these proteins have a common mechanism that regulates their mRNA translation. Iron influx increases the translation of these proteins via an iron-responsive element (IRE) RNA stem loop in their 5'untranlated region, while iron regulatory protein 1 (IRP1) controls and down regulates the iron-dependent translation. Messenger RNA IREs were modeled with RNA Shape. Binding of IRPs to IREs was measured by coupling biotin to the 5'UTR of the specific mRNA, incubating the construct with IRPs, precipitating the complex with Avidin beads, and visualizing the precipitate by Western blot. In vitro and in vivo (mice and human) measurements of APP and SNCA levels were executed either by immunoprecipitation, Elisa or Western blot. Posiphen increases binding of IRP1 to the IRE stem loop structure and further down regulates translation. We have data showing that Posiphen inhibits the translation of amyloid precursor protein (APP) and alpha synuclein (SNCA). We also have data showing that Posiphen inhibits their translation in a number of tissue culture cells, in normal, trisomic and transgenic mice, as well as in humans (MCI patients). At ICAD we want to present our newest data showing translational regulation via the 5'UTR IRE/IRP1 interaction for prions and superoxide dismutase (SOD) and further down regulation with Posiphen in vitro and in vivo. Our data shows that neurotoxic aggregating proteins, such as APP, SNCA, Prions and SOD have a regulatory element in their 5'UTR that is responsible for the amount of protein translated by the ribosome. This regulatory element consists of an IRE stem loop structure that when binding iron upregulates translation, while when binding IRP1 down regulates translation. Posiphen further inhibits the translation of these mRNAs by the ribosomes, because it increases the affinity of IRP1 binding to the IRE.