title: Soluble oligomeric Abeta disrupts the protein kinase C signaling pathway.
abstract: Alzheimer's disease (AD) is characterized by selective neurodegeneration of neurons involved in cognitive function. Current hypothesis for AD etiology needs to be reconsidered because fibrillar Abeta cannot explain selective neurodegeneration. Recent evidence suggests oligomeric Abeta may be more relevant to AD etiology. Here we show signaling disruption induced by oligomeric Abeta. Using the MTT assay, NT2 showed greatest susceptibility to soluble oligomeric Abeta. In the kinase assay, treatment with either monomeric Abeta or fibrillar Abeta evoked no response in PKA, PKC and TK. Oligomeric Abeta treatment, however, inactivated membranous PKC but activated cytosolic PKC in NT2 within 24 h. Our data suggest that oligomeric Abeta may cause selective neurodegeneration through a PKC signaling, distinctive from fibrillar Abeta.
authors.affiliation: Jinis Biopharmaceuticals Co., 452-32, Jang-Dong, Chonju, Chonbuk 561-360, Republic of Korea.
authors.forename: Hyeon-Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Jeong-Hak
authors.initials: JH
authors.lastname: Kim
authors.forename: Soo-Cheon
authors.initials: SC
authors.lastname: Chae
authors.forename: Yeong-Chul
authors.initials: YC
authors.lastname: Park
authors.forename: Keun-Sang
authors.initials: KS
authors.lastname: Kwon
authors.forename: Seong-Tshool
authors.initials: ST
authors.lastname: Hong
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D001932:Brain Neoplasms / Q000503:physiopathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009447:Neuroblastoma / Q000503:physiopathology; D011493:Protein Kinase C / Q000187:drug effects* / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D016229:Amyloid beta-Peptides; D013778:Tetrazolium Salts; D013844:Thiazoles; D011505:Protein-Tyrosine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; C022616:thiazolyl blue