Soluble oligomeric Abeta disrupts the protein kinase C signaling pathway.
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.
Kim
Hyeon-Jin
HJ
Jinis Biopharmaceuticals Co., 452-32, Jang-Dong, Chonju, Chonbuk 561-360, Republic of Korea.
Kim
Jeong-Hak
JH
Chae
Soo-Cheon
SC
Park
Yeong-Chul
YC
Kwon
Keun-Sang
KS
Hong
Seong-Tshool
ST
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
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