title: NAP and ADNF-9 protect normal and Down's syndrome cortical neurons from oxidative damage and apoptosis.
abstract: NAP (Asn-Ala-Pro-Val-Ser-Ile-Pro-Gln, single letter code: NAPVSIPQ) and ADNF-9 (activity-dependent neurotrophic factor-9; Ser-Ala-Leu-Leu-Arg-Ser-Ile-Pro-Ala; single letter code: SALLRSIPA) are peptides derived from naturally occurring glial proteins that have shown neuroprotection in rodent model systems. Here, the neuroprotective activity of ADNF-9 and NAP was tested in two human models of neuronal degeneration in culture mediated by oxidative stress: normal human cortical neurons treated with H2O2 and Down's syndrome (DS) cortical neurons. Incubation of normal cortical neurons with 50 microM H2O2 for 1 hour resulted in morphological and structural changes consistent with neuronal degeneration and loss of viability of more than 60% of the neurons present in the culture. Addition of ADNF-9 or NAP at femtomolar concentrations resulted in significant increases in survival of normal neurons treated with H2O2. Femtomolar concentrations of ADNF-9 or NAP exhibited a similar neuroprotective efficacy, comparable to the antioxidant N-tert-butyl-2-sulpho-phenylnitrone at 100 microM (s-PBN). Treatment of DS cortical neurons with ADNF-9 or NAP resulted in a significant increase in neuronal survival as well as reduction of degenerative morphological changes. The results suggest that ADNF-9 and NAP possess potent neuroprotective properties against oxidative damage in human neurons that may be useful to preserve neuronal function and prevent neuronal death associated with chronic neurodegenerative disorders.
authors: Department of Neurobiology and Behavior, University of California, Irvine, CA 92697, USA. jbuscigl@uci.edu
authors: Jorge
authors: J
authors: Busciglio
authors: Alejandra
authors: A
authors: Pelsman
authors: Pablo
authors: P
authors: Helguera
authors: Osnat
authors: O
authors: Ashur-Fabian
authors: Albert
authors: A
authors: Pinhasov
authors: Douglas E
authors: DE
authors: Brenneman
authors: Illana
authors: I
authors: Gozes
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D004314:Down Syndrome / Q000188:drug therapy / Q000378:metabolism*; D005333:Fetus; D006801:Humans; D051379:Mice; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use; D009842:Oligopeptides / Q000502:physiology* / Q000627:therapeutic use; D018384:Oxidative Stress / Q000502:physiology*
chemical_list: D018696:Neuroprotective Agents; D009842:Oligopeptides; C410622:activity-dependent neurotrophic factor; C425904:davunetide