TOXIC EFFECTS OF BETA-AMYLOID(25-35) ON IMMORTALIZED RAT-BRAIN ENDOTHELIAL-CELL - PROTECTION BY CARNOSINE, HOMOCARNOSINE AND BETA-ALANINE

The effect of a truncated form of the neurotoxin beta-amyloid peptide (A beta 25-35) on rat brain vascular endothelial cells (RBE4 cells) wa s studied in cell culture. Toxic effects of the peptide were seen at 2 00 mu g/ml A beta using a mitochondrial dehydrogenase activity (MTT) r eduction assay, lactate dehydrogenase release and glucose consumption. Cell damage could be prevented completely at 200 mu g/ml A beta and p artially at 300 mu g/ml A beta, by the dipeptide carnosine. Carnosine is a naturally occurring dipeptide found at high levels in brain tissu e and innervated muscle of mammals including humans. Agents which shar e properties similar to carnosine, such as beta-alanine, homocarnosine , the anti-glycating agent aminoguanidine, and the antioxidant superox ide dismutase (SOD), also partially rescued cells, although not as eff ectively as carnosine. We postulate that the mechanism of carnosine pr otection lies in its anti-glycating and antioxidant activities, both o f which are implicated in neuronal and endothelial cell damage during Alzheimer's disease. Carnosine may therefore be a useful therapeutic a gent. (C) 1998 Elsevier Science Ireland Ltd.