Neuroprotective activity of acetyl-L-carnitine: studies in vitro.
The neuroprotective properties of acetyl-L-carnitine (ALCAR) were investigated in primary cell cultures from rat hippocampal formation and cerebral cortex of 17-day-old rat embryos. Chronic exposure to ALCAR (10-50 microM for 10 days) reduced the cell mortality induced by 24 hr fetal calf serum deprivation. Protection was partial when the neuronal cells, chronically treated with ALCAR (50 microM), were exposed to glutamate (0.25-1 mM) and kainic acid (250-500 microM) for 24 hr. The neurotoxicity induced by N-methyl-D-aspartate (NMDA, 250 microM) was attenuated by the acute co-exposure with ALCAR (1 mM), the chronic treatment with ALCAR (50 microM) significantly reduced the neuronal death induced by NMDA (0.25-1 mM). Cell mortality was also investigated in ALCAR-treated hippocampal cultures chronically treated with beta-amyloid fragment 25-35. ALCAR appeared to have neuroprotective activity. This suggests an explanation of the positive results obtained with ALCAR in the treatment of Alzheimer's disease.
Forloni
G
G
Unit of Neurobiology of Alzheimer, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
Angeretti
N
N
Smiroldo
S
S
D000108:Acetylcarnitine / Q000494:pharmacology* / Q000627:therapeutic use; D000544:Alzheimer Disease / Q000188:drug therapy; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000633:toxicity; D000818:Animals; D001790:Blood Physiological Phenomena; D002417:Cattle; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000196:embryology; D003470:Culture Media / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates / Q000633:toxicity; D018698:Glutamic Acid; D006624:Hippocampus / Q000166:cytology* / Q000196:embryology; D006801:Humans; D007608:Kainic Acid / Q000037:antagonists & inhibitors / Q000633:toxicity; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000633:toxicity; D009474:Neurons / Q000187:drug effects*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000633:toxicity; D051381:Rats
D016229:Amyloid beta-Peptides; D003470:Culture Media; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D018698:Glutamic Acid; D016202:N-Methylaspartate; D000108:Acetylcarnitine; D007608:Kainic Acid