title: Nonsteroidal anti-inflammatory drugs attenuate amyloid-β protein-induced actin cytoskeletal reorganization through Rho signaling modulation.
abstract: Amyloid-β protein (Aβ) neurotoxicity occurs along with the reorganization of the actin-cytoskeleton through the activation of the Rho GTPase pathway. In addition to the classical mode of action of the non-steroidal anti-inflammatory drugs (NSAIDs), indomethacin, and ibuprofen have Rho-inhibiting effects. In order to evaluate the role of the Rho GTPase pathway on Aβ-induced neuronal death and on neuronal morphological modifications in the actin cytoskeleton, we explored the role of NSAIDS in human-differentiated neuroblastoma cells exposed to Aβ. We found that Aβ induced neurite retraction and promoted the formation of different actin-dependent structures such as stress fibers, filopodia, lamellipodia, and ruffles. In the presence of Aβ, both NSAIDs prevented neurite collapse and formation of stress fibers without affecting the formation of filopodia and lamellipodia. Similar results were obtained when the downstream effector, Rho kinase inhibitor Y27632, was applied in the presence of Aβ. These results demonstrate the potential benefits of the Rho-inhibiting NSAIDs in reducing Aβ-induced effects on neuronal structural alterations.
authors.affiliation: Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, AP 70-228, 04510, México, DF, Mexico.
authors.forename: Patricia
authors.initials: P
authors.lastname: Ferrera
authors.affiliation: Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, AP 70-228, 04510, México, DF, Mexico.
authors.forename: Angélica
authors.initials: A
authors.lastname: Zepeda
authors.affiliation: Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, AP 70-228, 04510, México, DF, Mexico. carias@unam.mx.
authors.forename: Clorinda
authors.initials: C
authors.lastname: Arias
mesh_terms: D000199:Actins / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003599:Cytoskeleton / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D010446:Peptide Fragments / Q000633:toxicity*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D000199:Actins; D016229:Amyloid beta-Peptides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D054460:rho-Associated Kinases
keywords: Actin cytoskeleton; Aβ toxicity; Ibuprofen; Indomethacin; Rho signaling