In vitro model of neurotoxicity of Aβ 1–42 and neuroprotection by a pentapeptide: irreversible events during the first hour

Abstract

The cell biology of Alzheimer's disease (AD) is characterized mainly by the neurodegeneration caused by the β-amyloid (Aβ) peptides and by the formation of neurofibrillary tangles. The initial events of neurodegeneration in the brain tissue include synaptic dysfunction and axonopathy. Aβ-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 Aβ on neuroblastoma cells. Aβ 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 Aβ 1–42 to the cells. These rapid events indicate that Aβ might induce neurodegeneration even at an early stage of Aβ-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 Aβ 1–42.

Keywords

• β-Amyloid
• Neurite degeneration
• Neuroblastoma cells
• Aggregation
• Neuroprotection