In vitro model of neurotoxicity of Abeta 1-42 and neuroprotection by a pentapeptide: irreversible events during the first hour.
The cell biology of Alzheimer's disease (AD) is characterized mainly by the neurodegeneration caused by the beta-amyloid (Abeta) peptides and by the formation of neurofibrillary tangles. The initial events of neurodegeneration in the brain tissue include synaptic dysfunction and axonopathy. Abeta-induced axonopathy and neurite degeneration were studied in vitro on differentiated human-derived neurotypic SH-SY5Y cells. Different methods were used to investigate the mechanism of action of aggregated Abeta on neuroblastoma cells. Abeta 1-42 aggregated for 1 h induced irreversible changes in the neurite morphology. Change of tau hyperphosphorylation and cell viability (cytoplasmic redox state and active membrane uptake) was irreversible during the first hour after the addition of Abeta 1-42 to the cells. These rapid events indicate that Abeta might induce neurodegeneration even at an early stage of Abeta-cell contact. A novel pentapeptide LPYFD-amide, an analog of Soto's LPFFD, significantly decreased neurite degeneration, tau aggregation, and cell viability reduction induced by Abeta 1-42.
Datki
Zsolt
Z
Department of Medical Chemistry, University of Szeged, Szeged, Hungary. datkiz@yahoo.com
Papp
Rita
R
Zádori
Dénes
D
Soós
Katalin
K
Fülöp
Lívia
L
Juhász
Anna
A
Laskay
Gábor
G
Hetényi
Csaba
C
Mihalik
Erzsébet
E
Zarándi
Márta
M
Penke
Botond
B
D000544:Alzheimer Disease / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000633:toxicity*; D045744:Cell Line, Tumor; D006801:Humans; D008855:Microscopy, Electron, Scanning; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000378:metabolism; D009454:Neurofibrils / Q000187:drug effects / Q000648:ultrastructure; D009498:Neurotoxins / Q000633:toxicity; D010446:Peptide Fragments / Q000627:therapeutic use*; D010766:Phosphorylation; D013997:Time Factors
D016229:Amyloid beta-Peptides; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D010446:Peptide Fragments