NAP and ADNF-9 protect normal and Down's syndrome cortical neurons from oxidative damage and apoptosis.
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.
Busciglio
Jorge
J
Department of Neurobiology and Behavior, University of California, Irvine, CA 92697, USA. jbuscigl@uci.edu
Pelsman
Alejandra
A
Helguera
Pablo
P
Ashur-Fabian
Osnat
O
Pinhasov
Albert
A
Brenneman
Douglas E
DE
Gozes
Illana
I
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*
D018696:Neuroprotective Agents; D009842:Oligopeptides; C410622:activity-dependent neurotrophic factor; C425904:davunetide