Oligomeric aggregates of amyloid beta peptide 1-42 activate ERK/MAPK in SH-SY5Y cells via the alpha 7 nicotinic receptor

• Published in: Neurochemistry international 2009-12, Vol.55 (8), p.796-801
• Main Authors: Young, Kirk F, Pasternak, Stephen H, Rylett, RJane
• Format: Article
• Language: English
• ISSN: 0197-0186
• DOI: 10.1016/j.neuint.2009.08.002

The production and aggregation of amyloid beta peptides (A beta ) has been linked to the development and progression of Alzheimer's disease. It is apparent that the various structural forms of A beta can affect cell signalling pathways and the activity of neurons differently. In this study, we investigated the effects of oligomeric and fibrillar aggregates of A beta 1-42 (A beta 42) and non-aggregated peptide upon activation of the ERK/MAPK signalling pathway. In SH-SY5Y cells, acute exposure to oligomeric A beta 42 led to phosphorylation of ERK1/2 at concentrations as low as 1 nM and up to 100 nM. These changes were detected as early as 5 min following exposure to 100 nM oligomeric A beta 42, reaching a maximum level after 10 min. Phosphorylation of ERK1/2 subsequently declined to and remained at basal levels after 30 min to 2 h of exposure. Fibrillar aggregates of A beta 42 did not significantly induce phosphorylation of ERK1/2 and non-aggregated A beta 42 did not activate the pathway. The effects of oligomeric A beta 42 to increase ERK phosphorylation above basal levels were inhibited by MLA, a specific antagonist of the alpha 7 nAChR. U0126, an inhibitor of MEK, the upstream activator of ERK1/2, completely blocked induction of ERK1/2 phosphorylation. Oligomeric aggregates of A beta 42 are the principal structural form of the peptide that activates ERK/MAPK in SH-SY5Y cells and these effects are mediated by the alpha 7 nAChR.