Anticonvulsants attenuate amyloid β-peptide neurotoxicity, Ca2+ deregulation, and cytoskeletal pathology

Robert J. Mark, J. Wesson Ashford, Y. Goodman, Mark P. Mattson

Research output: Contribution to journalArticle

Abstract

Increasing evidence supports the involvement of amyloid β-peptide (Aβ) and an excitotoxic mechanism of neuronal injury in the pathogenesis of Alzheimer's disease. However, approaches aimed at preventing Aβ toxicity and neurofibrillary degeneration are undeveloped. We now report that anticonvulsants (carbamazepine, phenytoin, and valproic acid) can protect cultured rat hippocampal neurons againsts Aβ- and glutamate-induced injury. Each of the anticonvulsant attentuated the elevated of intracellular free calcium levels [(Ca2+)i] elicited by Aβ or glutamate suggesting that their neuroprotective mechanism of action involved stabilization of [Ca2+]i. These compounds were effective at clinically relevant concentrations (carbamazepine, 100 nM-10 μM; phenytoin, 100 nM-1 μM; valproic acid, 100 nM-100 μM). The anticonvulsants suppressed glutamate-induced alterations in tau and ubiquitin immunoreactivities. Compounds that stabilize [Ca2+]i may afford protection against the kinds of insults believed to underlie neuronal injury in Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)187-198
Number of pages12
JournalNeurobiology of Aging
Volume16
Issue number2
DOIs
StatePublished - 1995
Externally publishedYes

Fingerprint

Amyloid
Anticonvulsants
Glutamic Acid
Carbamazepine
Valproic Acid
Phenytoin
Pathology
Peptides
Alzheimer Disease
Wounds and Injuries
Ubiquitin
Calcium
Neurons

Keywords

  • Alzheimer's disease
  • Anticonvulsant
  • Calcium
  • Carbamazepine
  • Fura-2
  • Glutamate
  • Hippocampus
  • Microtubule-associated protein
  • Neurofibrillary tangle
  • Phenytoin
  • Phosphorylation
  • Tau
  • Valproic acid

ASJC Scopus subject areas

  • Aging
  • Developmental Biology
  • Geriatrics and Gerontology
  • Clinical Neurology
  • Neuroscience(all)
  • Biological Psychiatry
  • Developmental Neuroscience
  • Neurology
  • Psychology(all)

Cite this

Anticonvulsants attenuate amyloid β-peptide neurotoxicity, Ca2+ deregulation, and cytoskeletal pathology. / Mark, Robert J.; Wesson Ashford, J.; Goodman, Y.; Mattson, Mark P.

In: Neurobiology of Aging, Vol. 16, No. 2, 1995, p. 187-198.

Research output: Contribution to journalArticle

Mark, Robert J. ; Wesson Ashford, J. ; Goodman, Y. ; Mattson, Mark P. / Anticonvulsants attenuate amyloid β-peptide neurotoxicity, Ca2+ deregulation, and cytoskeletal pathology. In: Neurobiology of Aging. 1995 ; Vol. 16, No. 2. pp. 187-198.
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