Visualisation of co-localisation in Ab42-administered neuroblastoma cells reveals lysosome damage and autophagosome accumulation related to cell death

Soura, Violetta, Stewart-Parker, Maris, Williams, Thomas L, Ratnayaka, Arjuna, Atherton, Joe, Gorringe, Kirsti, Tuffin, Jack, Darwent, Elisabeth, Rambaran, Roma, Klein, William, Lacor, Pascale, Staras, Kevin, Thorpe, Julian and Serpell, Louise (2012) Visualisation of co-localisation in Ab42-administered neuroblastoma cells reveals lysosome damage and autophagosome accumulation related to cell death. Biochemical Journal, 441 (2). pp. 579-590. ISSN 0264-6021

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Abstract

Aβ42 [amyloid-β 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 Aβ42 oligomers to a neuroblastoma (SH-SY5Y) cell line results in a reduction in survival, and that Aβ42 enters the cells prior to cell death. Immunoconfocal and immunogold electron microscopy reveal the path of the Aβ42 with time through the endosomal system and shows that it accumulates in lysosomes. A 24 h incubation with Aβ results in cells that have damaged lysosomes showing signs of enzyme leakage, accumulate autophagic vacuoles and exhibit severely disrupted nuclei. Endogenous Aβ is evident in the cells and the results of the present study suggest that the addition of Aβ oligomers disrupts a crucial balance in Aβ conformation and concentration inside neuronal cells, resulting in catastrophic effects on cellular function and, ultimately, in cell death.

Item Type: Article
Schools and Departments: School of Life Sciences > Biochemistry
Depositing User: Louise Serpell
Date Deposited: 26 Oct 2012 13:08
Last Modified: 05 Dec 2013 08:51
URI: http://sro.sussex.ac.uk/id/eprint/18452
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