【文章名】Visualization of co-localization in A beta 42-administered neuroblastoma cells reveals lysosome damage and autophagosome accumulation related to cell death
Visualization of co-localization in A beta 42-administered neuroblastoma cells reveals lysosome damage and autophagosome accumulation related to cell death
[摘要]：A beta 42 [amyloid-beta peptide-(1-42)] plays a central role in Alzheimer's disease and is known to have a detrimental effect on neuronal cell function and survival when assembled into an oligomeric form. In the present study we show that administration of freshly prepared A beta 42 oligomers to a neuroblastoma (SH-SY5Y) cell line results in a reduction in survival, and that A beta 42 enters the cells prior to cell death. Immunoconfocal and immunogold electron microscopy reveal the path of the A beta 42 with time through the endosomal system and shows that it accumulates in lysosomes. A 24 h incubation with A beta results in cells that have damaged lysosomes showing signs of enzyme leakage, accumulate autophagic vacuoles and exhibit severely disrupted nuclei. Endogenous A beta is evident in the cells and the results of the present study suggest that the addition of A beta oligomers disrupts a crucial balance in A beta conformation and concentration inside neuronal cells, resulting in catastrophic effects on cellular function and, ultimately, in cell death.
