Cytochalasins Protect Hippocampal Neurons Against Amyloid β‐Peptide Toxicity: Evidence that Actin Depolymerization Suppresses Ca2+ Influx

Katsutoshi Furukawa, Mark P. Mattson

Research output: Contribution to journalArticlepeer-review

45 Citations (Scopus)

Abstract

Abstract: Increasing data suggest that the amyloid β‐peptide (Aβ), which accumulates in the brains of Alzheimer's victims, plays a role in promoting neuronal degeneration. Cell culture studies have shown that Aβ can be neurotoxic and recent findings suggest that the mechanism involves destabilization of cellular calcium homeostasis. We now report that cytochalasin D, a compound that depolymerizes actin microfilaments selectively, protects cultured rat hippocampal neurons against Aβ neurotoxicity. Cytochalasin D was effective at concentrations that depolymerized actin (10–100 nM). The elevation of [Ca2+]i induced by Aβ, and the enhancement of [Ca2+]i responses to glutamate in neurons exposed to Aβ, were markedly attenuated in neurons pretreated with cytochalasin D. The protective effect of cytochalasin D appeared to result from a specific effect on actin filaments and reduction in calcium influx, because cytochalasin E, another actin filament‐disrupting agent, also protected neurons against Aβ toxicity; the microtubule‐disrupting agent colchicine was ineffective; cytochalasin D did not protect neurons against the toxicity of hydrogen peroxide. These findings suggest that actin filaments play a role in modulating [Ca2+]i responses to neurotoxic insults and that depolymerization of actin can protect neurons against insults relevant to the pathogenesis of Alzheimer's disease.

Original languageEnglish
Pages (from-to)1061-1068
Number of pages8
JournalJournal of Neurochemistry
Volume65
Issue number3
DOIs
Publication statusPublished - 1995 Sep

Keywords

  • Actin microfilaments
  • Alzheimer's disease
  • Amyloid
  • Calcium
  • Cytochalasin
  • Glutamate
  • Neurotoxicity
  • Phalloidin

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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