The action of acetyl-L-carnitine on the neurotoxicity evoked by amyloid fragments and peroxide on primary rat cortical neurones.
The amyloid beta-peptides have been implicated in the excitotoxic mechanism of neuronal injury in the pathogenesis of Alzheimer's disease. In this paper we examine the effect of different amyloid fragments (beta A1-40, A1-28, and A25-35), as well as potential neuroprotective compounds on rat cortical neuron viability. Exposure of neurones to beta A25-35 or A1-40 at concentrations as low as 1 microgram/ml inhibited, significantly, the MTT response and this level of inhibition was similar after 24-h or three-day exposure. Furthermore, the level of inhibition was not affected by the presence or absence of 5% horse serum in the medium. Preexposure (10 min) of neurones to ALC at concentrations of 0.1, 1, 5, and 10 mM attenuated the inhibition of the MTT response caused by beta A25-35 (50 micrograms/ml) in serum free medium for 24 h. The treatment of cells with vitamin E (100 microM), catalase (4 mg/ml), NGF (0.1 and 10 ng/ml), or cycloheximide (0.1 microgram/ml) significantly restored the MTT response that was inhibited by beta A25-35. The mechanism for the protective actions of these compounds against beta A25-35 toxicity is not clear but may involve free radical scavenger action and preservation of energy production, although other mechanisms, especially for ALC, such as a direct effect on A-beta interaction with charged anionic phospholipids and/or stabilizing action on membranes, are also possible.
Virmani
M A
MA
Research & Development Department, Sigma-tau HealthScience s.p.a., Via Treviso 4, 00040 Pomezia, Italy. ashraf.virmani@sigma-tau.it
Caso
V
V
Spadoni
A
A
Rossi
S
S
Russo
F
F
Gaetani
F
F
D000108:Acetylcarnitine / Q000494:pharmacology*; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex; D004622:Embryo, Mammalian; D006861:Hydrogen Peroxide / Q000633:toxicity; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018697:Nootropic Agents / Q000494:pharmacology*; D016877:Oxidants / Q000633:toxicity; D010446:Peptide Fragments / Q000633:toxicity*; D051381:Rats
D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D018697:Nootropic Agents; D016877:Oxidants; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D000108:Acetylcarnitine; D006861:Hydrogen Peroxide