NAP and ADNF-9 Protect Normal and Downs Syndrome Cortical Neurons from Oxidative Damage and Apoptosis
Jorge Busciglio, Alejandra Pelsman, Pablo Helguera, Osnat Ashur-Fabian, Albert Pinhasov, Douglas E. Brenneman and Illana Gozes
Pages 1091-1098 (8)
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 Downs syndrome (DS) cortical neurons. Incubation of normal cortical neurons with 50 μM 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 Ntert- butyl-2-sulpho-phenylnitrone at 100 μM (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.
neuroprotection, VIP Receptors, PAC1 receptor, Alzheimer's disease, NAP-binding ligand
Department of Neurobiology and Behavior, University of California, Irvine, CA 92697, USA.