Enhanced toxicity and cellular binding of a modified amyloid β peptide with a methionine to valine substitution

Abstract

The amyloid β peptide (Aβ) is toxic to neuronal cells, and it is probable that this toxicity is responsible for the progressive cognitive decline associated with Alzheimer's disease. However, the nature of the toxic Aβ species and its precise mechanism of action remain to be determined. It has been reported that the methionine residue at position 35 has a pivotal role to play in the toxicity of Aβ. We examined the effect of mutating the methionine to valine in Aβ42 (AβM35V). The neurotoxic activity of AβM35V on primary mouse neuronal cortical cells was enhanced, and this diminished cell viability occurred at an accelerated rate compared with Aβ42. AβM35V binds Cu2+ and produces similar amoun..