Protective and rescuing abilities of IGF-I and some putative free radical scavengers against beta-amyloid-inducing toxicity in neurons.
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.
Doré
S
S
Douglas Hospital Research Center, McGill University, Montreal, Quebec, Canada.
Bastianetto
S
S
Kar
S
S
Quirion
R
R
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000544:Alzheimer Disease / Q000378:metabolism / Q000628:therapy; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D005419:Flavonoids / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D020441:Ginkgo biloba; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010936:Plant Extracts; D051381:Rats; D000096983:Ginkgo Extract
D000276:Adjuvants, Immunologic; D016229:Amyloid beta-Peptides; D003687:Dehydroepiandrosterone; D005419:Flavonoids; D016166:Free Radical Scavengers; D007334:Insulin-Like Growth Factor I; D010936:Plant Extracts; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract