Ciliary neurotrophic factor fused to a protein transduction domain retains full neuroprotective activity in the absence of cytokine-like side effects

dc.creatorRezende, AC
dc.creatorPeroni, D
dc.creatorVieira, AS
dc.creatorRogerio, F
dc.creatorTalaisys, RL
dc.creatorCosta, FTM
dc.creatorLangone, F
dc.creatorSkaper, SD
dc.creatorNegro, A
dc.date2009
dc.dateJUN
dc.date2014-11-15T16:43:27Z
dc.date2015-11-26T17:20:52Z
dc.date2014-11-15T16:43:27Z
dc.date2015-11-26T17:20:52Z
dc.date.accessioned2018-03-29T00:08:26Z
dc.date.available2018-03-29T00:08:26Z
dc.identifierJournal Of Neurochemistry. Wiley-blackwell Publishing, Inc, v. 109, n. 6, n. 1680, n. 1690, 2009.
dc.identifier0022-3042
dc.identifierWOS:000266268400011
dc.identifier10.1111/j.1471-4159.2009.06091.x
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/55924
dc.identifierhttp://www.repositorio.unicamp.br/handle/REPOSIP/55924
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/55924
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1283236
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionCiliary neurotrophic factor (CNTF) is a multifunctional cytokine that can regulate the survival and differentiation of many types of developing and adult neurons. CNTF prevents the degeneration of motor neurons after axotomy and in mouse mutant progressive motor neuronopathy, which has encouraged trials of CNTF for human motor neuron disease. Given systemically, however, CNTF causes severe side effects, including cachexia and a marked immune response, which has limited its clinical application. The present work describes a novel approach for administering recombinant human CNTF (rhCNTF) while conserving neurotrophic activity and avoiding deleterious side effects. rhCNTF was fused to a protein transduction domain derived from the human immunodeficiency virus-1 TAT (transactivator) protein. The resulting fusion protein (TAT-CNTF) crosses the plasma membrane within minutes and displays a nuclear localization. TAT-CNTF was equipotent to rhCNTF in supporting the survival of cultured chicken embryo dorsal root ganglion neurons. Local or subcutaneous administration of TAT-CNTF, like rhCNTF rescued motor neurons from death in neonatal rats subjected to sciatic nerve transection. In contrast to subcutaneous rhCNTF, which caused a 20-30% decrease in body weight in neonatal rats between postnatal days 2 and 7 together with a considerable fat mobilization in brown adipose tissue, TAT-CNTF lacked such side effects. Together, these results indicate that rhCNTF fused with the protein transduction domain/TAT retains neurotrophic activity in the absence of CNTFs cytokine-like side effects and may be a promising candidate for the treatment of motor neuron and other neurodegenerative diseases.
dc.description109
dc.description6
dc.description1680
dc.description1690
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionASV [05/57335-6]
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionFAPESP [05/54613-7, 04/14210-8]
dc.descriptionCNPq [473909/2004-9]
dc.descriptionASV [05/57335-6]
dc.languageen
dc.publisherWiley-blackwell Publishing, Inc
dc.publisherMalden
dc.publisherEUA
dc.relationJournal Of Neurochemistry
dc.relationJ. Neurochem.
dc.rightsfechado
dc.rightshttp://olabout.wiley.com/WileyCDA/Section/id-406071.html
dc.sourceWeb of Science
dc.subjectciliary neurotrophic factor
dc.subjectfusion protein
dc.subjectmotor neuron
dc.subjectneuroprotection
dc.subjectprotein transduction domain
dc.subjectweight loss
dc.subjectAxotomized Facial Motoneurons
dc.subjectProgressive Motor Neuronopathy
dc.subjectAmyotrophic-lateral-sclerosis
dc.subjectSciatic-nerve Transection
dc.subjectAcute-phase Response
dc.subjectIn-vivo
dc.subjectNeuronotrophic Factor
dc.subjectFactor Prevents
dc.subjectNeonatal Rat
dc.subjectFactor Cntf
dc.titleCiliary neurotrophic factor fused to a protein transduction domain retains full neuroprotective activity in the absence of cytokine-like side effects
dc.typeArtículos de revistas


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