Protective and rescuing abilities of IGF-I and some putative free radical scavengers against beta-amyloid-inducing toxicity in neurons

Ann N Y Acad Sci. 1999;890:356-64. doi: 10.1111/j.1749-6632.1999.tb08015.x.

Abstract

beta-Amyloid (A beta) peptides are most likely involved in the neurodegenerative process occurring in Alzheimer's Disease (AD) and are enriched in senile plaques. The mechanisms of A beta toxicity are not clear but likely involve free radicals and apoptosis. Much interest is currently aiming at developing effective approaches to block A beta toxicity in order to slow down disease progression. In that context, we are particularly interested in studying the role of insulin-like growth factors, particularly IGF-I and purported free radical scavengers including a Gingko biloba extract (EGb761) as blocker of A beta toxicity in a simple in vitro model of hippocampal primary cultures. We observed that both IGF-I and EGb761 are unique in that they are able not only to protect but even to rescue neurons against A beta toxicity. These results are summarized here and possible mechanisms of action are discussed to explain the protective properties of these two classes of agents.

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / therapy
  • Amyloid beta-Peptides / antagonists & inhibitors*
  • Amyloid beta-Peptides / toxicity
  • Animals
  • Cell Survival / drug effects
  • Cells, Cultured
  • Dehydroepiandrosterone / pharmacology*
  • Drug Evaluation, Preclinical
  • Flavonoids / pharmacology*
  • Free Radical Scavengers / pharmacology*
  • Ginkgo biloba
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Insulin-Like Growth Factor I / pharmacology*
  • Neurons / drug effects*
  • Neurons / metabolism
  • Plant Extracts*
  • Rats

Substances

  • Adjuvants, Immunologic
  • Amyloid beta-Peptides
  • Flavonoids
  • Free Radical Scavengers
  • Plant Extracts
  • Ginkgo biloba extract
  • Dehydroepiandrosterone
  • Insulin-Like Growth Factor I