acetyl-aspartyl-glutamyl-valyl-aspartal and Acute-Disease

The amyloid-beta precursor protein (APP) is directly and efficiently cleaved by caspases during apoptosis, resulting in elevated amyloid-beta (A beta) peptide formation. The predominant site of caspase-mediated proteolysis is within the cytoplasmic tail of APP, and cleavage at this site occurs in hippocampal neurons in vivo following acute excitotoxic or ischemic brain injury. Caspase-3 is the predominant caspase involved in APP cleavage, consistent with its marked elevation in dying neurons of Alzheimer's disease brains and colocalization of its APP cleavage product with A beta in senile plaques. Caspases thus appear to play a dual role in proteolytic processing of APP and the resulting propensity for A beta peptide formation, as well as in the ultimate apoptotic death of neurons in Alzheimer's disease.

Topics: Acute Disease; Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Amyloid Precursor Protein Secretases; Amyloidosis; Animals; Apoptosis; Aspartic Acid; Aspartic Acid Endopeptidases; Brain Diseases; Camptothecin; Caspase 3; Caspases; Cysteine Proteinase Inhibitors; Endopeptidases; Enzyme Inhibitors; Enzyme Precursors; Excitatory Amino Acid Agonists; Hippocampus; Humans; In Situ Nick-End Labeling; Kainic Acid; Leukemia, Erythroblastic, Acute; Male; Mice; Mice, Inbred C57BL; Mutation; Neurons; Oligopeptides; Rabbits; Rats; Rats, Wistar; Sweden; Tumor Cells, Cultured