Valbuena, Paola C.

[["dc.bibliographiccitation.firstpage","61"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Brain Research"],["dc.bibliographiccitation.lastpage","66"],["dc.bibliographiccitation.volume","1082"],["dc.contributor.author","Dietz, Gunnar P. H."],["dc.contributor.author","Valbuena, Paola C."],["dc.contributor.author","Dietz, Birgit"],["dc.contributor.author","Meuer, Katrin"],["dc.contributor.author","Müller, Patrick"],["dc.contributor.author","Weishaupt, Jochen H."],["dc.contributor.author","Bähr, Mathias"],["dc.date.accessioned","2017-09-07T11:53:10Z"],["dc.date.available","2017-09-07T11:53:10Z"],["dc.date.issued","2006"],["dc.description.abstract","Glial-cell-line-derived neurotrophic factor (GDNF) promotes mesencephalic dopaminergic neuronal survival in several in vitro and in vivo models. As the demise of dopaminergic neurons is the cause for Parkinson's disease (PD) symptoms, GDNF is a promising agent for its treatment However, this neurotrophin is unable to cross the blood-brain barrier, which has complicated its clinical use. Therefore, ways to deliver GDNF into the central nervous system in an effective manner are needed. The HIV-1-Tat-derived cell-penetrating peptide (CPP) provides a means to deliver fusion proteins into the brain. We generated a fusion protein between the 11 amino acid CPP of Tat and the rat GDNF mature protein to deliver GDNF across the blood-brain barrier. We showed previously that Tat-GDNF enhances the neuroprotective effect of GDNF in in vivo models for nerve trauma and ischemia. Here, we tested its effect in a subchronic scheme of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) application into the mouse as a model for PD to evaluate the effect of Tat-GDNF fusion protein in dopaminergic neuron survival. We showed that the fusion protein did indeed reach the dopaminergic neurons. However, the in vivo application of Tat-GDNF did not provide neuroprotection of dopaminergic neurons, as revealed by immunohistochemistry and counting of the number of tyrosine-hydroxylase-immunoreactive neurons in the substantia nigra pars compacta. Possibly, GDNF does protect nigro-striatal projections of those neurons that survive MPTP treatment but does not increase the number of surviving dopaminergic neurons. A concomitant treatment of Tat-GDNF with an anti-apoptotic Tat-fusion protein might be beneficial. (c) 2006 Elsevier B.V. All rights reserved."],["dc.identifier.doi","10.1016/j.brainres.2006.01.083"],["dc.identifier.gro","3143709"],["dc.identifier.isi","000236931400007"],["dc.identifier.pmid","16703672"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1253"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0006-8993"],["dc.subject","Cell-penetrating peptide (CPP); Protein transduction domain (PTD); Blood–brain barrier; Neuroprotection; MPTP mouse model"],["dc.title","Application of a blood-brain-barrier-penetrating form of GDNF in a mouse model for Parkinson's disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","757"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Journal of Neurochemistry"],["dc.bibliographiccitation.lastpage","765"],["dc.bibliographiccitation.volume","104"],["dc.contributor.author","Dietz, G. P. H."],["dc.contributor.author","Stockhausen (née Peters), K. V."],["dc.contributor.author","Dietz, B."],["dc.contributor.author","Falkenburger, B. H."],["dc.contributor.author","Valbuena, P."],["dc.contributor.author","Opazo, F."],["dc.contributor.author","Lingor, P."],["dc.contributor.author","Meuer, K."],["dc.contributor.author","Weishaupt, J. H."],["dc.contributor.author","Schulz, J. B."],["dc.contributor.author","Bähr, M."],["dc.date.accessioned","2017-09-07T11:48:48Z"],["dc.date.available","2017-09-07T11:48:48Z"],["dc.date.issued","2008"],["dc.description.abstract","The anti-apoptotic Bcl-x(L) is a promising agent to prevent neurodegeneration in Parkinson's disease, which is characterized by a demise of dopaminergic neurons. We linked Bcl-x(L) to a peptide that allows its delivery across biological membranes and the blood-brain barrier. We tested the fusion protein in two models of Parkinson's Disease. Cell-permeable Bcl-x(L) protected neuroblastoma cells from the selective neurotoxin 1-methyl-4-phenylpyridinium. Furthermore, its systemic application in aged mice protected dopaminergic neurons following administration of MPTP as revealed by counting of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra pars compacta. Hence, we present that a cell-permeable form of an anti-apoptotic protein can be delivered to CNS neurons through its systemic application, and we provide the proof that the delivery of this protein to the CNS neurons effectively prevents neuronal cell death in models of chronic neurodegenerative diseases."],["dc.identifier.doi","10.1111/j.1471-4159.2007.05028.x"],["dc.identifier.gro","3143353"],["dc.identifier.isi","000252322600015"],["dc.identifier.pmid","17995935"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/858"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0022-3042"],["dc.title","Membrane-permeable Bcl-x(L) prevents MPTP-induced dopaminergic neuronal loss in the substantia nigra"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]