N-PEP-12--a novel peptide compound that protects cortical neurons in culture against different age and disease associated lesions.
The neuroprotective potency of N-PEP-12, a novel, proprietary compound consisting of biopeptides and amino acids was investigated. Lesion models have been applied in neuronal cultures of embryonic chicken cortex, pre-treated with N-PEP-12 from the first day onwards. On day 8 in vitro neurons were lesioned and cell viability was measured 24 and 48 hours later. To simulate acute brain ischemia, cytotoxic hypoxia was induced by sodium cyanide or by iodoacetate and excitotoxicity by L-glutamate. Ionomycin for up to 48 hours induced calcium overload. The cytoskeleton was disrupted by addition of colchicine. N-PEP-12 shows dose-dependent neuroprotection in all different models. The effect size depends on the recovery time but also on the extent of the lesion. In cases of mild to moderate lesion pronounced dose-dependent effects could be demonstrated. This indicates that chronic exposure to N-PEP-12 is able to prevent neuronal cell death associated to conditions occurring during normal aging and neurological disorders like ischemic stroke, hypoxia, brain trauma, or AD.
Windisch
M
M
JSW-Research Forschungslabor GmbH, Graz, Austria. mwindisch@jswresearch.com
Hutter-Paier
B
B
Grygar
E
E
Doppler
E
E
Moessler
H
H
D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D001927:Brain Diseases / Q000188:drug therapy; D015687:Cell Hypoxia / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016922:Cellular Senescence; D002540:Cerebral Cortex / Q000166:cytology*; D002642:Chick Embryo; D002645:Chickens; D003078:Colchicine / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D007461:Iodoacetates / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000494:pharmacology; D012966:Sodium Cyanide / Q000494:pharmacology
D000596:Amino Acids; D004791:Enzyme Inhibitors; D007461:Iodoacetates; C501962:N-PEP-12; D018696:Neuroprotective Agents; D009498:Neurotoxins; D018698:Glutamic Acid; D012966:Sodium Cyanide; D003078:Colchicine