Linked Life Data

15478191

Source:http://linkedlifedata.com/resource/pubmed/id/15478191

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2004-10-27
pubmed:abstractText
Amyotrophic lateral sclerosis (ALS) is the most common fatal motor neuron disease, affecting mostly middle-aged people. There are no curative therapies for ALS. Several lines of evidence have supported the notion that the proapoptotic property of familial ALS (FALS)-linked mutant Cu/Zn-superoxide dismutase-1 (SOD1) genes may play an important role in the pathogenesis of some FALS cases. Here we found that activity-dependent neurotrophic factor (ADNF), a neurotrophic factor originally identified to have the anti-Alzheimer's disease (AD) activity, protected against neuronal cell death caused by FALS-linked A4T-, G85R- and G93R-SOD1 in a dose-responsive fashion. Notably, ADNF-mediated complete suppression of SOD1 mutant-induced neuronal cell death occurs at concentrations as low as 100 fM. ADNF maintains the neuroprotective activity even at concentrations of more than 1 nM. This is in clear contrast to the previous finding that ADNF loses its protective activity against neurotoxicity induced by AD-relevant insults, including some familial AD genes and amyloid beta peptide at concentrations of more than 1 nM. Characterization of the neuroprotective activity of ADNF against cell death caused by SOD1 mutants revealed that CaMKIV and certain tyrosine kinases are involved in ADNF-mediated neuroprotection. Moreover, in vivo studies showed that intracerebroventricularly administered ADNF significantly improved motor performance of G93A-SOD1 transgenic mice, a widely used model of FALS, although survival was extended only marginally. Thus, the neuroprotective activity of ADNF provides a novel insight into the development of curative drugs for ALS.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0360-4012
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
78
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
542-52
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:15478191-Age of Onset, pubmed-meshheading:15478191-Amyotrophic Lateral Sclerosis, pubmed-meshheading:15478191-Animals, pubmed-meshheading:15478191-Blotting, Western, pubmed-meshheading:15478191-Cell Count, pubmed-meshheading:15478191-Cell Death, pubmed-meshheading:15478191-Cell Line, Transformed, pubmed-meshheading:15478191-Disease Models, Animal, pubmed-meshheading:15478191-Dose-Response Relationship, Drug, pubmed-meshheading:15478191-Drug Interactions, pubmed-meshheading:15478191-Embryo, Mammalian, pubmed-meshheading:15478191-Enzyme Inhibitors, pubmed-meshheading:15478191-Female, pubmed-meshheading:15478191-Humans, pubmed-meshheading:15478191-Male, pubmed-meshheading:15478191-Mice, pubmed-meshheading:15478191-Mice, Transgenic, pubmed-meshheading:15478191-Mutagenesis, pubmed-meshheading:15478191-Neurons, pubmed-meshheading:15478191-Oligopeptides, pubmed-meshheading:15478191-Psychomotor Performance, pubmed-meshheading:15478191-Rats, pubmed-meshheading:15478191-Superoxide Dismutase, pubmed-meshheading:15478191-Time Factors, pubmed-meshheading:15478191-Transfection
pubmed:year
2004
pubmed:articleTitle
Neuroprotective effect of activity-dependent neurotrophic factor against toxicity from familial amyotrophic lateral sclerosis-linked mutant SOD1 in vitro and in vivo.
pubmed:affiliation
Department of Pharmacology, KEIO University School of Medicine, Tokyo, Japan.
pubmed:publicationType
Journal Article, Comparative Study, In Vitro, Research Support, Non-U.S. Gov't