Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson's disease

The sirtuins are members of the histone deacetylase family of proteins that participate in a variety of cellular functions and play a role in aging. We identified a potent inhibitor of sirtuin 2 (SIRT2) and found that inhibition of SIRT2 rescued alpha-synuclein toxicity and modified inclusion morphology in a cellular model of Parkinson's disease. Genetic inhibition of SIRT2 via small interfering RNA similarly rescued alpha-synuclein toxicity. Furthermore, the inhibitors protected against dopaminergic cell death both in vitro and in a Drosophila model of Parkinson's disease. The results suggest a link between neurodegeneration and aging.     

Selective Removal of Lead from Calcareous Polluted Soils using the Ca-EDTA Salt

EDTA is a powerful chelating reagentwhich has been often proposed for the decontaminationof lead polluted soils. Despite the pronouncedselectivity of this reagent for Pb, a low degree ofutilisation is observed when treating calcareoussoils, due to the co-dissolution of calcite. Thisstudy demonstrates that it is possible to suppresscalcite dissolution and optimise the degree of EDTAutilisation, using the calcium salt of EDTA, insteadof the common sodium salts. Initial experiments, whichwere carried out mixing pure cerrusite (PbCO₃)with a Na₂CaEDTA solution, have shown that Pb isquantitatively solubilised, while calcium precipitatesin the form of aragonite. The performance of thisreagent in the decontamination of soils has beentested on a soil sample from Lavrion (Greece)containing 7.3–8.8% of Ca and heavily polluted withPb at levels up to 3.5%. The parameters which weretested include the reaction time, the stoichiometricexcess of Na₂CaEDTA with respect to Pb and theeffect of successive treatment stages with freshNa₂CaEDTA solutions. The experimental resultshave shown that long reaction times, exceeding 24 hr, are required in order to obtain sufficient Pbremoval and preserve the calcium content of the soil.Lead extraction increases from 27 to 40% prolongingthe reaction time from 1 to 24 hr atNa₂CaEDTA/Pb = 1 mol/mol. Increasing theNa₂CaEDTA/Pb molar ratio from 1 to 3.5 mol/mol,enhances the dissolution of Pb from 40 to 53%, whichis not proportional to the stoichiometric excesssupplied. The efficiency of Pb removal is maximized,up to 75%, applying three successive leaching stages.The major benefit of Na₂CaEDTA in comparison withthe disodium EDTA salt is the preservation of soilcalcite. The initial calcium content of the soil wasfound to increase by 4% using the Ca salt; on thecontrary, the treatment with Na₂H₂EDTA undersimilar experimental conditions has resulted indissolving 27% of soil Ca.     

Removal of Heavy Metals from Calcareous Contaminated Soils by EDTA Leaching

The performance of EDTA for the treatment of calcareous soils contaminated with heavy metals from mining and smelting activities was evaluated in this study. Soil samples containing variable levels of contamination, from 500 to 35 000 mg kg^-1 Pb and 700 to 20 000 mg kg^-1 Zn, were subjected to EDTA treatment and the extraction of heavy metals was found to vary, ranging between 50 and 98% for Pb and 50 to 100% for Zn. Total residual concentrations were above the limits set by regulatory authorities; leachable metals, however, were efficiently removed and treated soils were all acceptable in terms of toxicity. The effect of EDTA concentration and pulp density was studied on a soil sample containing 12 000 mg kg^-1 Pb and 10 000 mg kg^-1 Zn. Heavy metals removal was improved at low pulp densities and when EDTA concentration was increased from 0.025 to 0.25 M. The tetrasodium salt Na₄-EDTA was found to be less effective for metals removal compared to the disodium salt Na₂-EDTA, though applied at higher concentrations. This experimental work has also demonstrated the great importance of soil matrix for the overall evaluation of the EDTA leaching as a cost effective remedial option. The simultaneous dissolution of calcite was found to consume approximately 90% of the available EDTA. It was thus concluded that for the treatment of calcareous soils the design criteria and cost estimations should be based on the calcite content of the soil.