Calz and coauthors demonstrate that reasch Furosemide intraneuronal amyloid accumulation in neurons increases vulnerability to cell death upon oxygenglucose deprivation, and interestingly, exposure of neurons to astrocyteconditioned culture media confers protection.We cannot highlight all of them because of space limitations, but we would like to mention a couple of standout papers from. The authors propose that this trait could provide a reliable biomarker of the disease.Sue was a visionary pioneer who was unsurpassed in her ability to harness model systems to explore fundamental biology and elucidate mechanisms of human disease.Her fearlessness led her to champion the humble budding yeast as a simple, yet powerful new model to study the cell biology underpinning neurodegeneration.We suspect that these insights will soon reach the clinic.Science. Nature. Dis. Model. Mech. smsinahceM sledoMes aesiD Experimental models show that metformin inhibits the growth of certain neoplasms by cell autonomous mechanisms such as activation of AMP kinase with secondary inhibition of protein synthesis or by an indirect mechanism involving reduction in gluconeogenesis leading to a decline in insulin levels and reduced proliferation of insulinresponsive cancers.Here, we show that metformin attenuates paraquatinduced elevations in reactive oxygen species, and related DNA damage and mutations, but has no effect on similar changes induced by H, indicating a reduction in endogenous ROS production.Our results reveal previously unrecognized inhibitory effects of metformin on ROS production and somatic cell mutation, providing a novel mechanism for the reduction in cancer risk reported to be associated with exposure to this drug.While details of its mechanism of action remain an active area of research, there is prior evidence that its primary effect is in mitochondria, where it interferes with respiratory complex I and reduces ATP production. In type II diabetes, metformin action in the liver results in inhibition of gluconeogenesis, reducing blood glucose concentration, and secondarily reducing the elevated insulin levels characteristic of this condition.Although these epidemiologic data are retrospective and must be considered hypothesis generating rather than conclusive, they have motivated laboratory research to evaluate antineoplastic activities of metformin.Several in vitro and in vivo experimental systems have shown that metformin reduces growth rates of experimental tumors. One class of proposed mechanisms is indirect, and involves the well documented action of metformin on the liver, which results in reduction of the hyperglycemia and hyperinsulinemia characteristic of type II diabetes, leading to reduced insulin receptor activation and reduced proliferation of the subset of neoplasms for which hyperinsulinemia provides a growth advantage.However, these mechanisms may not be sufcient to account for the cancer risk reduction reported in pharmacoepidemiologic investigations or observed experimentally.Twentyfour hours later, the medium was changed to FBS DMEM and selected groups were treated with mmolL metformin for hours at which time groups were treated with either mmolL HO or mmolL paraquat for hours.Then cells were washed times in PBS with BSA and incubated with a goat antimouse secondary antibody for hour at room temperature.Then, electroporation cuvette and pulsed during ms at V in the presence of mg of plasmid DNA.Cells were then plated and treated with mmolL metformin or vehicle for hours.