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 journalArticle

Abstract

β/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 β/A4 toxicity to a human nerve cell line. Human SH-SY5Y cells respond to aggregated β/A4 with changes in cell shape, membrane blebbing, antigenic modification, loss of attachment to the substrate, and cell death. β/A4 peptides require aggregation for maximum toxic effects, as cellular degeneration is evoked by aggregated β/A4 1-42 and 4-41 cysteine but not by monomeric β/A4 1-40. Aged (pre-aggregated) β/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 β/A4. Signaling pathways leading to β/A4-evoked neurodegeneration thus are under experimental control, becoming complete only when proliferating cells withdraw from the cell cycle and develop a postmitotic phenotype.

Original languageEnglish (US)
Pages (from-to)377-385
Number of pages9
JournalJournal of Neuroscience Research
Volume39
Issue number4
DOIs
StatePublished - 1994
Externally publishedYes

Fingerprint

Neuroblastoma
Peptides
Cell Line
Cell Shape
Poisons
Blister
Cysteine
Epitopes
Cell Cycle
Alzheimer Disease
Cell Death
Up-Regulation
Cell Membrane
Phenotype
Neurons
Brain

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Lambert, M. P., Stevens, G., Sabo, S., Barber, K., Wang, G., Wade, W., ... Klein, W. L. (1994). β/A4-evoked degeneration of differentiated SH-SY5Y human neuroblastoma cells. Journal of Neuroscience Research, 39(4), 377-385. https://doi.org/10.1002/jnr.490390404

β/A4-evoked degeneration of differentiated SH-SY5Y human neuroblastoma cells. / Lambert, M. P.; Stevens, G.; Sabo, S.; Barber, K.; Wang, G.; Wade, W.; Krafft, G.; Snyder, S.; Holzman, T. F.; Klein, W. L.

In: Journal of Neuroscience Research, Vol. 39, No. 4, 1994, p. 377-385.

Research output: Contribution to journalArticle

Lambert, MP, Stevens, G, Sabo, S, Barber, K, Wang, G, Wade, W, Krafft, G, Snyder, S, Holzman, TF & Klein, WL 1994, 'β/A4-evoked degeneration of differentiated SH-SY5Y human neuroblastoma cells', Journal of Neuroscience Research, vol. 39, no. 4, pp. 377-385. https://doi.org/10.1002/jnr.490390404
Lambert, M. P. ; Stevens, G. ; Sabo, S. ; Barber, K. ; Wang, G. ; Wade, W. ; Krafft, G. ; Snyder, S. ; Holzman, T. F. ; Klein, W. L. / β/A4-evoked degeneration of differentiated SH-SY5Y human neuroblastoma cells. In: Journal of Neuroscience Research. 1994 ; Vol. 39, No. 4. pp. 377-385.
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