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Titolo:
Neuron-specific expression of therapeutic proteins: Evaluation of different cellular promoters in recombinant adenoviral vectors
Autore:
Kugler, S; Meyn, L; Holzmuller, H; Gerhardt, E; Isenmann, S; Schulz, JB; Bahr, M;
Indirizzi:
Univ Tubingen, Dept Neurol, Neuroregenerat Lab, D-72076 Tubingen, Germany Univ Tubingen Tubingen Germany D-72076 at Lab, D-72076 Tubingen, Germany Univ Tubingen, Dept Neurol, Neurodegenerat Lab, D-72076 Tubingen, Germany Univ Tubingen Tubingen Germany D-72076 at Lab, D-72076 Tubingen, Germany
Titolo Testata:
MOLECULAR AND CELLULAR NEUROSCIENCE
fascicolo: 1, volume: 17, anno: 2001,
pagine: 78 - 96
SICI:
1044-7431(200101)17:1<78:NEOTPE>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
CEREBELLAR GRANULE NEURONS; MEDIATED GENE-TRANSFER; HIPPOCAMPAL-NEURONS; APOPTOSIS; DEATH; BRAIN; CULTURE; RAT; SYSTEM; CELLS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
35
Recensione:
Indirizzi per estratti:
Indirizzo: Kugler, S Univ Tubingen, Dept Neurol, Neuroregenerat Lab, Verfugungsgebaude,Morgenstelle 15, D-72076 Tubingen, Germany Univ Tubingen Verfugungsgebaude,Morgenstelle 15 Tubingen Germany D-72076
Citazione:
S. Kugler et al., "Neuron-specific expression of therapeutic proteins: Evaluation of different cellular promoters in recombinant adenoviral vectors", MOL CELL NE, 17(1), 2001, pp. 78-96

Abstract

In order to achieve neuron-restricted expression of antiapoptotic proteins, cellular promoters were investigated for their expression profiles in thecontext of adenoviral vectors. Both the synapsin 1 gene and the tubulin alpha1 gene promoters were strictly neuron specific in cocultures of primary neurons with their essential feeder cells. The neuron-specific enolase genepromoter exhibited only weak activity in cultured hippocampal neurons and was not neuron specific in preparations of cerebellar granule cells. By attaining virtually 100% transduction efficiency we were able to generate "quasi-transgenic" primary neuron cultures using both differentiated and completely undifferentiated hippocampal neurons. In a functional assay, we used the synapsin promoter to evaluate the effect of Bcl-X-L, overexpression on potassium-withdrawal-induced apoptosis of cerebellar granule neurons. We found nearly complete inhibition of caspase-9 and -3 activation and apoptosis,indicating a major role for mitochondrial pathways in this paradigm of neuronal cell death. The excellent suitability of the synapsin promoter as a strong panneuronal promoter was further demonstrated by its restricted neuronal activity in various brain regions of adult rats in vivo.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 18/01/20 alle ore 01:58:41