Neuron-specific expression of therapeutic proteins: Evaluation of different cellular promoters in recombinant adenoviral vectors
2001 | journal article; research paper. A publication with affiliation to the University of Göttingen.
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Neuron-specific expression of therapeutic proteins: Evaluation of different cellular promoters in recombinant adenoviral vectors
Kügler, S. ; Meyn, L.; Holzmüller, H.; Gerhardt, E. ; Isenmann, S.; Schulz, J. B. & Bähr, M. (2001)
Molecular and Cellular Neuroscience, 17(1) pp. 78-96. DOI: https://doi.org/10.1006/mcne.2000.0929
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- Authors
- Kügler, S. ; Meyn, L.; Holzmüller, H.; Gerhardt, E. ; Isenmann, S.; Schulz, J. B. ; Bähr, M.
- Abstract
- In order to achieve neuron-restricted expression of antiapoptotic proteins, cellular promoters were investigated for their expression profiles in the context 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 gene promoter 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.
- Issue Date
- 2001
- Journal
- Molecular and Cellular Neuroscience
- ISSN
- 1044-7431
- Language
- English