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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 Serpell
Aß42 [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 Journal

ISSN

0264-6021

Publisher

Portland Press

Issue

2

Volume

441

Page range

579-590

Department affiliated with

  • Neuroscience Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2012-02-06

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