Visualization of co-localization in Aβ42-administered neuroblastoma cells reveals lysosome damage and autophagosome accumulation related to cell death

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 Staras, Julian Thorpe, Louise C. Serpell*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

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 (SHSY5Y) cell line results in a reduction in survival, and that Aβ42 enters the cells prior to cell death. Immunoconfocal and immunogold electronmicroscopy reveal the path of theAβ42 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.

Original languageEnglish (US)
Pages (from-to)579-590
Number of pages12
JournalBiochemical Journal
Volume441
Issue number2
DOIs
StatePublished - Jan 15 2012

Keywords

  • Alzheimer's disease
  • Amyloid-β peptide-(1-42) (Aβ42)
  • Autophagosome
  • Lysosome
  • Oligomer

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Visualization of co-localization in Aβ42-administered neuroblastoma cells reveals lysosome damage and autophagosome accumulation related to cell death'. Together they form a unique fingerprint.

Cite this