| Autor: |
Bolton SJ; Department of Neuroscience Research, SmithKline Beecham Pharmaceuticals plc, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK. sjb73@leicester.ac.uk, Jones DN, Darker JG, Eggleston DS, Hunter AJ, Walsh FS |
| Jazyk: |
angličtina |
| Zdroj: |
The European journal of neuroscience [Eur J Neurosci] 2000 Aug; Vol. 12 (8), pp. 2847-55. |
| DOI: |
10.1046/j.1460-9568.2000.00171.x |
| Abstrakt: |
Investigation of normal and pathological diseases of the central nervous system (CNS) has been hampered by the inability to effectively manipulate protein function in vivo. In order to address this important topic, we have evaluated the ability of penetratin, a novel cell-permeable peptide consisting of a 16-amino acid sequence derived from a Drosophila homeodomain protein, to act as a carrier system to introduce a cargo into brain cells. Fluorescently tagged penetratin was injected directly into rat brain, either into the striatum or the lateral ventricles, and rats were perfusion-fixed 24 h later in order to assess the brain response to the peptide. Immunohistochemistry following intrastriatal injection showed that injection of 10 microg penetratin caused neurotoxic cell death and triggered recruitment of inflammatory cells in a dose-dependent fashion. Doses of 1 microg or less resulted in reduced toxicity and recruitment of inflammatory cells, but interestingly, there was some spread of the penetratin. Injections of an inactive peptide sequence, derived from the same homeodomain, caused little toxicity but could still, however, trigger an inflammatory response. Intraventricular injections showed extensive inflammatory cell recruitment but minimal spread of either peptide. These results suggest that a dose of 1 microg of penetratin peptide is suitable for directing agents to small, discrete areas of the brain and as such is an interesting new system for analysing CNS function. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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