β/A4‐evoked degeneration of differentiated SH‐SY5Y human neuroblastoma cells

M. P. Lambert, G. Stevens, S. Sabo, K. Barber, G. Wang, W. Wade, G. Krafft, S. Snyder, T. F. Holzman, W. L. Klein

Research output: Contribution to journalArticlepeer-review

Abstract

ß/A4 peptides are known to induce neurodegeneration in cultures of rat brain cells and rat neural cell lines (Yankner et al: Science 250:279–282, 1990; Behl et al: Biochem Biophys Res Commun 186:944–950, 1992). The current data show that these peptides induce similar neurodegeneration in SH‐SY5Y neuroblastoma cells, extending characterization of ß/A4 toxicity to a human nerve cell line. Human SH‐SY5Y cells respond to aggregated ß/A4 with changes in cell shape, membrane blebbing, antigenic modification, loss of attachment to the substrate, and cell death. ß/A4 peptides require aggregation for maximum toxic effects, as cellular degeneration is evoked by aggregated ß/A4 1‐42 and 4‐41 cysteine but not by monomeric ß/A4 1‐40. Aged (pre‐aggregated) ß/A4 1‐40 also evoked neurodegeneration. Antigenic changes comprise upregulation of Alzheimer's‐type tau epitopes, recognized by the PHF‐1 and Alz‐50 monoclonals. These particular changes in tau support the connectivity between this in vitro model and mechanisms leading to neurodegeneration in Alzheimer's disease. A significant feature of the SH‐SY5Y response is that cells must be differentiated before they become sensitive to the degeneration evoked by ß/A4. Signaling pathways leading to ß/A4‐evoked neurodegeneration thus are under experimental control, becoming complete only when proliferating cells withdraw from the cell cycle and develop a postmitotic phenotype. © 1994 Wiley‐Liss, Inc.

Original languageEnglish (US)
Pages (from-to)377-385
Number of pages9
JournalJournal of neuroscience research
Volume39
Issue number4
DOIs
StatePublished - Nov 1 1994

Keywords

  • AD‐tau
  • Alz‐50
  • PHF‐1
  • retinoic acid differentiation
  • β amyloid

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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