Gamma-carbolines derivatives as promising agents for the development of pathogenic therapy for proteinopathy

Uncontrolled protein aggregation, accompanied by the formation of specific inclusions, is a major component of the pathogenesis of many common neurodegenerative diseases known as proteinopathies. The intermediate products of this aggregation are toxic to neurons and may be lethal. The development strategy of pathogenic therapy for proteinopathy is based on the design of drugs capable of both inhibiting proteinopathy progression and increasing the survival of affected neurons. The results of a decade-long research effort at leading Russian and international laboratories have demonstrated that Dimebon (Latrepirdine), as well as a number of its derivatives from a gamma-carboline group, show a strong neuroprotective effect and can modulate the course of a neurodegenerative process in both in vitro and in vivo model systems. The accumulated data indicate that gamma-carbolines are promising compounds for the development of pathogenic therapy for proteinopathies

Gamma-carbolines derivatives as promising agents for the development of pathogenic therapy for proteinopathy

Uncontrolled protein aggregation, accompanied by the formation of specific inclusions, is a major component of the pathogenesis of many common neurodegenerative diseases known as proteinopathies. The intermediate products of this aggregation are toxic to neurons and may be lethal. The development strategy of pathogenic therapy for proteinopathy is based on the design of drugs capable of both inhibiting proteinopathy progression and increasing the survival of affected neurons. The results of a decade-long research effort at leading Russian and international laboratories have demonstrated that Dimebon (Latrepirdine), as well as a number of its derivatives from a gamma-carboline group, show a strong neuroprotective effect and can modulate the course of a neurodegenerative process in both in vitro and in vivo model systems. The accumulated data indicate that gamma-carbolines are promising compounds for the development of pathogenic therapy for proteinopathies

The effectiveness of a new domestic carbohydrate-protein product in the practice of training of high class

<p>The effect of the use of the new course of the carbohydrate-protein product on the performance efficiency of skilled athletes (Greco-Roman). In the experiment involved 14 athletes aged 18-25 years who gave written consent to participate in the study. Developed and clinically tested a specialized carbohydrate-protein food product. The drink contains in its composition: glucose, sucrose, whey protein concentrate, creatine monohydrate, citrulline malate, mineral complex and ATP-lipid complex. The study was conducted in two micro-cycles (2 weeks). Athletes take a drink as follows: pre-workout (30-40 minutes) - 250 ml of the drink, after a training session during the recovery period - 250 ml of the drink. It is established that the use of the drink has a positive effect on the performance of athletes performance during the execution of a sub-maximal anaerobic power in the area of energy supply. Argues that course application beverage reduces the severity of manifestations of lactate acidosis after exercise by improving the utilization of lactate. Found a significant decrease in the concentration of lactate in the blood of athletes in the 7th minute of recovery in relation to the original data.</p

Molybdate partly mimics insulin-promoted metabolic effects in Drosophila melanogaster

Molybdenum-containing salts have been found to attenuate diabetes complications in mammals by affecting processes normally regulated by insulin and thus were believed to mimic insulin activity. In this study, we used a fruit fly model to test sodium molybdate, Na2MoO4, action in relation to insulin-promoted processes and toxicity. We studied how larval food supplementation with sodium molybdate affected levels of body carbohydrates and lipids in two-day old adult Drosophila melanogaster. Molybdate salt, in the concentrations used (0.025, 0.05, 0.5, 5, and 10 mM), showed low toxicity to fly larvae and slightly influenced development and the percentage of pupated animals. Additionally, sodium molybdate decreased the level of hemolymph glucose in males by 30%, and increased the level of hemolymph trehalose in flies of both sexes. These changes were accompanied by an increase in whole body trehalose and glycogen of about 30-90%. Although total lipid levels in flies of both sexes were depleted by 25%, an increased amount of triacylglycerides among total lipids was observed. These effects were not related to changes in food intake. Taken together, the present data let us suggest that sodium molybdate may at least partly mimic insulin-related effects in Drosophila

Exposure to sodium molybdate results in mild oxidative stress in Drosophila melanogaster

Objectives: The study was conducted to assess the redox status of Drosophila flies upon oral intake of insulin-mimetic salt, sodium molybdate (Na2MoO4). Methods: Oxidative stress parameters and activities of antioxidant and associated enzymes were analyzed in two-day-old D. melanogaster insects after exposure of larvae and newly eclosed adults to three molybdate levels (0.025, 0.5, or 10 mM) in the food. Results: Molybdate increased content of low molecular mass thiols and activities of catalase, superoxide dismutase, g

S-nitrosoglutathione-induced toxicity in Drosophila melanogaster: Delayed pupation and induced mild oxidative/nitrosative stress in eclosed flies

The toxicity of the nitric oxide donor S-nitrosoglutathione (GSNO) was tested on the Drosophila melanogaster model system. Fly larvae were raised on food supplemented with GSNO at concentrations of 1.0, 1.5 or 4.0. mM. Food supplementation with GSNO caused a developmental delay in the flies. Biochemical analyses of oxidative stress markers and activities of antioxidant and associated enzymes were carried out on 2-day-old flies that emerged from control larvae and larvae fed on food supplemented with GSNO. Larval exposure to GSNO resulted in lower activities of aconitase in both sexes and also lower activities of catalase and isocitrate dehydrogenase in adult males relative to the control cohort. Larval treatment wi