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| Biochemische in vivo - Modulation von Sialoglycokonjugaten
und deren biologische Konsequenzen Gagiannis, Daniel |
| Main title | Biochemische in vivo - Modulation von Sialoglycokonjugaten und deren biologische Konsequenzen |
| Title variations | Biochemical modulation of Sialoglycoconjugates and its biological consequences in vivo |
| Author(s) | Gagiannis, Daniel
Place of birth: Gera |
| 1. Referee | Prof. Dr. med. W. Reutter |
| Further Referee(s) | Prof. Dr. med. E. Köttgen Prof. Dr. rer. nat. S. Kelm |
| Classification (DDC) | 610 Medical sciences; Medicine |
| Summary | Sialic acids (Sia) play an important role during development, regeneration and pathogenesis of different diseases. The modification of cellular sialic acids by using synthetic precursors is called Biochemical Engineering. It allows the functional examination of the N-Acyl-side-chain with regard to expression, adhesion, proliferation and differentiation of the cell. In this work the distribution of natural Sia as well as the substance- and time-dependent changes of Sia after application of modified precursors were analysed in vivo for the first time. Thereby arose clear references to the organs in which a particularly high Sia metabolism takes place and which biological processes can be influenced specifically in vivo. Considering to the fact that Sia play an essential role in cell-cell- and cell-matrix-interactions, this is an important evidence for further research. Our results promise a further development to potentially pharmacological applications. We could demonstrate an exchange of natural Sia reaching 68% after only 45 days. Furthermore the investigation into side effects showed unobtrusive histochemical findings. Next to extensive pharmakokinetic data also regarding UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE)-deficient mice, approaches for possible clinical applications were explained. So we could demonstrate that application of N-Propanoylmannosamin leads to a reduced NCAM-Polysialylation and in consequence to a reduction of the metastatic potential. This might indicate new therapeutic options for several tumor types, e.g. alveolar rhabdomyosarkoma, undifferentiated neuroblastoma, anaplastic Wilms tumor, peripheral T-cell lymphoma and pancreatic carcinoma as well as any endocrine lung tumor. In the field of endocrinology and neurology impressive observations could be made, too. After a few days of treatment we could register significantly increased levels of testosterone and an increased spermatogenesis. Besides the possibility of direct application among patients with an innate or acquired testosterone deficiency, these results give the opportunity for a completely new possibility to influence pathophysiological processes in which glycoproteins are involved. It could be possible in near future to control the half-lives of peptide-hormones or transportation-proteins as well as the sensitivity of specific receptors through similar mechanisms. Moreover, a plenty of tests regarding behaviour showed a faster on-capacity but a reduced relearn-rate. Due to these experiments, skills for a further development of therapeutic methods against illnesses which are accompanied by disturbances of the synaptic plasticity were provided. Finally, we analyzed Myelin-associated proteins (MOG, MBP) concerning modifications. Combined with the current theory of pathogenesis, some results indicate anew therapeutic concept of Multiple Sclerosis without significant side effects. |
| Documents |
Dataobject from FUDISS_thesis_000000005055
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| Number of pages | 125 |
| FU Department | Department of Medicine - Charité - University Medicine Berlin |
| Year of publication | 2008 |
| Document type | Doctoral thesis |
| Media type/Format | Text |
| Language | German |
| Terms of use/Rights | Nutzungsbedingungen |
| Date of defense | 2008-09-19 |
| Created at | 2008-08-22 : 11:50:20 |
| Last changed | 2010-02-19 : 12:34:29 |
| Static URL | http://www.diss.fu-berlin.de/diss/receive/FUDISS_thesis_000000005055 |
| NBN | urn:nbn:de:kobv:188-fudissthesis000000005055-6 |
| Statistics | |
| E-mail address | gagiannis@email.de |
