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Titolo:
Complete sequence of a novel protein containing a femtomolar-activity-dependent neuroprotective peptide
Autore:
Bassan, M; Zamostiano, R; Davidson, A; Pinhasov, A; Giladi, E; Perl, O; Bassan, H; Blat, C; Gibney, G; Glazner, G; Brenneman, DE; Gozes, I;
Indirizzi:
TellAviv Univ, Sackler Sch Med, Dept Clin Biochem, IL-69978 Tel Aviv, Israe Tel Aviv Univ Tel Aviv Israel IL-69978 Biochem, IL-69978 Tel Aviv, Israe NICHD, Sect Dev & Mol Pharmacol, Dev Neurobiol Lab, NIH, Bethesda, MD USA NICHD Bethesda MD USA harmacol, Dev Neurobiol Lab, NIH, Bethesda, MD USA
Titolo Testata:
JOURNAL OF NEUROCHEMISTRY
fascicolo: 3, volume: 72, anno: 1999,
pagine: 1283 - 1293
SICI:
0022-3042(199903)72:3<1283:CSOANP>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
VASOACTIVE-INTESTINAL-PEPTIDE; E-DEFICIENT MICE; GROWTH-FACTOR PRECURSOR; CENTRAL-NERVOUS-SYSTEM; AMYLOID-BETA-PEPTIDE; ALZHEIMERS-DISEASE; APOLIPOPROTEIN-E; NEURONAL SURVIVAL; OXIDATIVE STRESS; FATTY NEUROPEPTIDE;
Keywords:
vasoactive intestinal peptide; apolipoprotein E; learning and memory; neuronal survival; molecular cloning; mRNA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
60
Recensione:
Indirizzi per estratti:
Indirizzo: Gozes, I TellAviv Univ, Sackler Sch Med, Dept Clin Biochem, IL-69978 Tel Aviv, Israe Tel Aviv Univ Tel Aviv Israel IL-69978 IL-69978 Tel Aviv, Israe
Citazione:
M. Bassan et al., "Complete sequence of a novel protein containing a femtomolar-activity-dependent neuroprotective peptide", J NEUROCHEM, 72(3), 1999, pp. 1283-1293

Abstract

The vulnerability of neurons and the irreversibility of loss make discoveries of neuroprotective compounds fundamentally important. Here, the complete coding sequence of a novel protein (828 amino acids, pl 5.99), derived from mouse neuroglial cells, is revealed. The sequence contained (1) a neuroprotective peptide, NAPVSIPQ, sharing structural and immunological homologies with the previously reported, activity-dependent neurotrophic factor; (2)a glutaredoxin active site; and (3) a zinc binding domain. Gene expressionwas enriched in the mouse hippocampus and cerebellum and augmented in the presence of the neuropeptide vasoactive intestinal peptide, in cerebral cortical astrocytes. In mixed neuron-astrocyte cultures, NAPVSIPQ provided neuroprotection at subfemtomolar concentrations against toxicity associated with tetrodotoxin (electrical blockade), the p-amyloid peptide (the Alzheimer's disease neurotoxin), N-methyl-D-aspartate (excitotoxicity), and the human immunodeficiency virus envelope protein. Daily NAPVSIPQ injections to newborn apolipoprotein E-deficient mice accelerated the acquisition of developmental reflexes and prevented short-term memory deficits. Comparative studies suggested that NAPVSIPQ was more efficacious than other neuroprotective peptides in the apolipoprotein E-deficiency model. A potential basis for rational drug design against neurodegeneration is suggested with NAPVSIPQ as a lead compound. The relative enrichment of the novel mRNA transcripts in the brain and the increases found in the presence of vasoactive intestinal peptide, an established neuroprotective substance, imply a role for the cloned protein in neuronal function.

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Documento generato il 01/12/20 alle ore 08:22:11