β-Amyloid-induced activation of Caspase-3 in primary cultures of rat neurons

It is known that beta-amyloid peptide (A beta) contributes to the neurodegeneration in Alzheimer's disease (AD) and operates through activation of an apoptotic pathway. Apoptotic signal is driven by a family of cysteine proteases called caspases. The beta-amyloid precursor protein (APP) is directly and efficiently cleaved by caspases during apoptosis, resulting in elevated beta-amyloid peptide formation. Cerebellar neurons from rat pups were treated with the aged A beta(25-35) at 1 and 5 mu M and fluorescence assays of caspase activity performed over 4 days. We observed an increase in caspase activity after 48 h treatment in both 1 and 5 mu M treated cells, then (72-96 h) caspase activity decreased to control values. The data presented support the hypothesis that A beta(25-35)-induced apoptosis is mediated by the activation of Caspase-3 and that this is a transient effect. (C) 2000 Published by Elsevier Science Ireland Ltd.