AN ADENOVIRUS ENCODING CUZNSOD PROTECTS CULTURED STRIATAL NEURONS AGAINST GLUTAMATE TOXICITY

SUPEROXIDE dismutase (SOD), a key enzyme in the detoxification of free radicals, catalyses the dismutation of superoxide O-2(.-) to oxygen a nd hydrogen peroxide (H2O2). It is therefore a promising candidate for gene transfer therapy of neurological diseases in which free radicals are thought to be involved. We have constructed a recombinant adenovi ral vector containing the human copper-zinc SOD cDNA. Using this vecto r we were able to drive the production of an active human copper-zinc SOD protein (hCuZnSOD) in various cell lines and primary cultures. Inf ection of striatal cells with a recombinant adenovirus expressing hCuZ nSOD protected these cells from glutamate-induced cell death.