Antisense strategy unravels tau proteins as molecular risk factors for glutamate-induced neurodegeneration

Marina Pizzi, Alessandra Valerio, Virginia Arrighi, Marco Belloni, Antonella Alberici, PierFranco Spano, Maurizio Memo

Research output: Contribution to journalArticlepeer-review

Abstract

1. We investigated the possible involvement of tau proteins in the neurotoxic process activated by glutamate using the oligonucleotide antisense strategy. 2. We found that pretreatment of granule cells with an antisense oligonucleotide of the tau gene completely prevented the increase in tau immunoreactivity induced by glutamate. 3. A significant amount of the tau antisense oligonucleotide (about 1 to 2% of total) was taken up by the cells and remained stable in the cells for at least 60 min. A dose-response study revealed that 25 μM tau antisense oligonucleotide was the most efficacious concentration in terms of prevention of glutamate-induced tau immunoreactivity increases, without affecting basal tau expression. Higher concentrations of tau oligonucleotide antisense reduced tau immunoreactivity in control cells. 4. Significantly, the concentration-response curve of glutamate for inducing neuronal death in cells pretreated with tau antisense oligonucleotide showed a shift to the right compared to those obtained in untreated or tau sense oligonucleotide-treated cells. 5. Since inhibition of tau synthesis does not completely prevent but only decreases the neuronal sensitivity to glutamate, it is tempting to speculate that accumulation of tau within the neuron in response to glutamate represents one of the molecular risk factors lowering the safety margin of neurons to excitotoxic-induced injury.

Original languageEnglish
Pages (from-to)569-578
Number of pages10
JournalCellular and Molecular Neurobiology
Volume14
Issue number5
DOIs
Publication statusPublished - Oct 1994

Keywords

  • cytoskeleton
  • excitatory amino acids
  • neurodegeneration
  • phosphorylation

ASJC Scopus subject areas

  • Neuroscience(all)
  • Genetics
  • Clinical Biochemistry
  • Cell Biology

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