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Visualization of co-localization in Aß42-administered neuroblastoma cells reveals lysosome damage and autophagosome accumulation related to cell death
journal contribution
posted on 2023-06-07, 21:19 authored by Violetta Soura, Maris Stewart-Parker, Thomas L Williams, Arjuna Ratnayaka, Joe Atherton, Kirsti Gorringe, Jack Tuffin, Elisabeth Darwent, Roma Rambaran, William Klein, Pascale Lacor, Kevin StarasKevin Staras, Louise SerpellLouise SerpellAß42 [amyloid-ß 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 Aß42 oligomers to a neuroblastoma (SH-SY5Y) cell line results in a reduction in survival, and that Aß42 enters the cells prior to cell death. Immunoconfocal and immunogold electron microscopy reveal the path of the Aß42 with time through the endosomal system and shows that it accumulates in lysosomes. A 24 h incubation with Aß results in cells that have damaged lysosomes showing signs of enzyme leakage, accumulate autophagic vacuoles and exhibit severely disrupted nuclei. Endogenous Aß is evident in the cells and the results of the present study suggest that the addition of Aß oligomers disrupts a crucial balance in Aß conformation and concentration inside neuronal cells, resulting in catastrophic effects on cellular function and, ultimately, in cell death.
History
Publication status
- Published
Journal
Biochemical JournalISSN
0264-6021Publisher
Portland PressExternal DOI
Issue
2Volume
441Page range
579-590Department affiliated with
- Neuroscience Publications
Full text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2012-02-06Usage metrics
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