|Title||Nonsteroidal anti-inflammatory drugs can lower amyloidogenic Abeta42 by inhibiting Rho.|
|Publication Type||Journal Article|
|Year of Publication||2003|
|Authors||Zhou Y, Su Y, Li B, Liu F, Ryder JW, Wu X, Gonzalez-DeWhitt PA, Gelfanova V, Hale JE, May PC, Paul SM, Ni B|
|Date Published||2003 Nov 14|
|Keywords||Amides, Amyloid beta-Peptides, Amyloid Precursor Protein Secretases, Animals, Anti-Inflammatory Agents, Non-Steroidal, Aspartic Acid Endopeptidases, Brain, Cell Line, Tumor, Endopeptidases, Enzyme Inhibitors, Guanosine Triphosphate, Humans, Ibuprofen, Intracellular Signaling Peptides and Proteins, Mice, Mice, Transgenic, Peptide Fragments, Polyisoprenyl Phosphates, Protein-Serine-Threonine Kinases, Pyridines, rho GTP-Binding Proteins, rho-Associated Kinases, rhoA GTP-Binding Protein, Sesquiterpenes, Signal Transduction, Sulindac, Transfection|
A subset of nonsteroidal anti-inflammatory drugs (NSAIDs) has been shown to preferentially reduce the secretion of the highly amyloidogenic, 42-residue amyloid-beta peptide Abeta42. We found that Rho and its effector, Rho-associated kinase, preferentially regulated the amount of Abeta42 produced in vitro and that only those NSAIDs effective as Rho inhibitors lowered Abeta42. Administration of Y-27632, a selective Rock inhibitor, also preferentially lowered brain levels of Abeta42 in a transgenic mouse model of Alzheimer's disease. Thus, the Rho-Rock pathway may regulate amyloid precursor protein processing, and a subset of NSAIDs can reduce Abeta42 through inhibition of Rho activity.