Suppression of PrPSc- and HIV-1 gp120 induced neuronal cell death by sulfated colominic acid

The scrapie prion protein (PrPSc) has been shown to induce apoptosis of rat cortical neurons in vitro. Here we demonstrate that the toxic effect displ ayed by PrPSc can be blocked by sulfated colominic acid (polymer of N-acety lneuraminic acid). This compound acts neuroprotectively at a concentration of greater than or equal to 0.3 mu g/ml when preincubated with the neurons or PrPSc. Rat cortical cells also undergo apoptosis after incubation with t he HIV-1 coat protein gp120 in vitro. This effect was abolished also by sul fated colominic acid when preincubated with the cells or gp120. Addition of 0.3 mu g/ml of compound resulted in an increase in cell viability by about 1.6 - 1.9-fold compared to cultures incubated for 18 h with 30 ng/ml of Pr PSc or 20 ng/ml of gp 120 alone (containing about 40% viable cells). Sulfat ed colominic acid does not act as antagonist of NMDA receptor channels at c oncentrations of up to 3 mu g/ml when co-administered with 100 mu g/ml of N MDA. It displayed a strong cytoprotective effect on human T lymphoblastoid CEM cells exposed to HIV-1; a 50% protection occurred after preincubation o f the cells with 0.43 mu g,/ml of compound. At the same concentration, the compound caused an inhibition of HIV-1-induced syncytium formation. Sulfate d colominic acid may be a promising compound for treatment of dementia caus ed by PrPSc and HIV-1 infections.