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Current Pharmaceutical Design
ISSN (Print): 1381-6128
ISSN (Online): 1873-4286
VOLUME: 13
ISSUE: 11
DOI: 10.2174/138161207780618957      Price:  $58









NAP and ADNF-9 Protect Normal and Downs Syndrome Cortical Neurons from Oxidative Damage and Apoptosis

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Author(s): Jorge Busciglio, Alejandra Pelsman, Pablo Helguera, Osnat Ashur-Fabian, Albert Pinhasov, Douglas E. Brenneman and Illana Gozes
Pages 1091-1098 (8)
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 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.
Keywords:
neuroprotection, VIP Receptors, PAC1 receptor, Alzheimer's disease, NAP-binding ligand
Affiliation:
Department of Neurobiology and Behavior, University of California, Irvine, CA 92697, USA.