Different amyloidogenic peptides share a similar mechanism of neurotoxicity involving reactive oxygen species and calcium

Mark P. Mattson, Yadong Goodman

Research output: Contribution to journalArticle

Abstract

The amyloid β-peptide (Aβ) that accumulates as insoluble plaques in the brains of Alzheimer's victims can be neurotoxic, by a mechanism that may involve generation of reactive oxygen species (ROS) and destabilization of cellular calcium homeostasis. We now provide evidence that the mechanism of neurotoxicity of two other amyloidogenic peptides (APs), human amylin and β2-microglobulin, also involves induction of ROS and elevation of [Ca2+]i. Human amylin, β2-microglobulin and Aβ1-40 all caused significant death of neurons in rat hippocampal cell cultures during 24-48h exposure periods. Rat amylin, a non-AP, was not neurotoxic. Each AP caused an elevation of rest [Ca2+]i during a 20 h exposure period, and promoted a sustained elevation of [Ca2+]i following exposure to glutamate which was significantly greater than controls. Each AP induced accumulation of ROS in neurons which preceded elevation of [Ca2+]i. Several antioxidants, including propyl gallate, vitamin E and the spin-trapping compound N-tert-butyl-α-phenylnitrone attenuated the elevation of [Ca2+]i and neurotoxicity induced by the peptides. The data indicate that different APs share a common mechanism of neurotoxicity involving free radical accumulation and destabilization of [Ca2+]i homeostasis.

Original languageEnglish (US)
Pages (from-to)219-224
Number of pages6
JournalBrain Research
Volume676
Issue number1
DOIs
StatePublished - Apr 3 1995
Externally publishedYes

Keywords

  • 2,7-Dichlorofluorescin
  • Alzheimer's disease
  • Amylin
  • Calcium
  • Fura-2
  • Hippocampus
  • Prion protein
  • Vitamin E
  • β2-Microglobulin

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology
  • Clinical Neurology
  • Neuroscience(all)

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