Role of phenylalanine 20 in Alzheimer's amyloid β-peptide (1-42)-induced oxidative stress and neurotoxicity

Debra Boyd-Kimball, Hafiz Mohmmad Abdul, Tanea Reed, Rukhsana Sultana, D. Allan Butterfield

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


Senile plaques are a hallmark of Alzheimer's disease (AD), a neurodegenerative disease associated with cognitive decline and aging. Aβ(1-42) is the primary component of the senile plaque in AD brain and has been shown to induce protein oxidation in vitro and in vivo. Oxidative stress is extensive in AD brain. As a result, Aβ(1-42) has been proposed to play a central role in the pathogenesis of AD; however, the specific mechanism of neurotoxicity remains unknown. Recently, it has been proposed that long distance electron transfer from methionine 35 to the Cu(II) bound at the N terminus of Aβ(1-42) occurs via phenylalanine 20. Additionally, it was proposed that substitution of phenylalanine 20 of Aβ(1-42) by alanine [Aβ(1-42)F20A] would lessen the neurotoxicity induced by Aβ(1-42). In this study, we evaluate the predictions of this theoretical study by determining the oxidative stress and neurotoxic properties of Aβ(1-42)F20A relative to Aβ(1-42) in primary neuronal cell culture. Aβ(1-42)F20A induced protein oxidation and lipid peroxidation similar to Aβ(1-42) but to a lesser extent and in a manner inhibited by pretreatment of neurons with vitamin E. Additionally, Aβ(1-42)F20A affected mitochondrial function similar to Aβ(1-42), albeit to a lesser extent. Furthermore, the mutation does not appear to abolish the ability of the native peptide to reduce Cu(II). Aβ(1-42)F20A did not compromise neuronal morphology at 24 h incubation with neurons, but did so after 48 h incubation. Taken together, these results suggest that long distance electron transfer from methionine 35 through phenylalanine 20 may not play a pivotal role in Aβ(1-42)-mediated oxidative stress and neurotoxicity.

Original languageEnglish
Pages (from-to)1743-1749
Number of pages7
JournalChemical Research in Toxicology
Issue number12
StatePublished - Dec 2004

ASJC Scopus subject areas

  • Toxicology


Dive into the research topics of 'Role of phenylalanine 20 in Alzheimer's amyloid β-peptide (1-42)-induced oxidative stress and neurotoxicity'. Together they form a unique fingerprint.

Cite this