STAUROSPORINE AND K-252 COMPOUNDS PROTECT HIPPOCAMPAL-NEURONS AGAINST AMYLOID BETA-PEPTIDE TOXICITY AND OXIDATIVE INJURY

Recent studies have shown that amyloid beta-peptide (A beta) can be directly neurotoxic by a mechanism related to secondary structure of the peptide, and mediated by free radical production and an increase in the concentration of intracellular free calcium ([Ca2+](i)). We now report that staurosporine and K-252 compounds, low molecular weight alkaloids of bacterial origin, can protect cultured rat hippocampal neurons against the toxicity of A beta in a concentration-dependent manner. The alkaloids also protected neurons against iron-induced (free radical-mediated) injury. Measurements of [Ca2+](i) using fura-2 imaging revealed that the elevation of [Ca2+](i) that occurred in response to long-term exposure to A beta was attenuated in neurons treated with staurosporine and K-252 compounds. These findings indicate that staurosporine and K-252 compounds can interupt a neurodegenerative pathway relevant to the pathophysiology of Alzheimer's disease.