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.
Sanders-Brown Research Center on Aging, University of Kentucky, Lexington 40536-0230.
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Goodman
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Mattson
D000470:Alkaloids / Q000494:pharmacology*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors*; D000818:Animals; D002227:Carbazoles / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D026121:Indole Alkaloids; D009474:Neurons / Q000187:drug effects*; D010084:Oxidation-Reduction; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D051381:Rats; D019311:Staurosporine
D000470:Alkaloids; D016229:Amyloid beta-Peptides; D002227:Carbazoles; D026121:Indole Alkaloids; C049985:staurosporine aglycone; D011493:Protein Kinase C; D019311:Staurosporine