Susanne Bürger

Spenden & Helfen

Curriculum vitae

Name Susanne Bürger
Place of birth Halle/Saale, Germany
Date of birth 18.July 1981
   
Since 2008 PhD. student, Paul Flechsig Institute for Brain Research, University of Leipzig, Germany, thesis title: Vascular Endothelial Growth Factor (VEGF) in ßamyloidogenesis, supported by the Alzheimer Forschung Initiative (AFI).
2007 Diploma in biology (M.S.) (final grade 1.6), Friedrich-Schiller University, Jena, Germany, thesis title: Analysis of the gene expression pattern of the wiring molecules of the semaphorin-, neuropilin-, plexin- family during the murine thalamocortical development, Junior research group of neurogenetics
2000-2006 Studies of biology, Friedrich-Schiller University, Jena, Germany, Major subjects: Neuroscience, Zoology, Cell biology and Immunobiology
 

Project description

The role of the Vascular Endothelial Growth Factor (VEGF) in processing of the β-amyloid precursor protein

There is some debate that Alzheimer´s disease (AD) may represent a vascular disorder that is caused by impaired cerebral perfusion. Ischemia and hypofusion have been shown to trigger accumulation and cleavage of the amyloid precursor protein (APP) into β-amyloid.
The upregulation of the angiogenic vesicular endothelial growth factor (VEGF) in response to hypoxic, ischemic or hypoglycemic stress as well as in brains of Alzheimer patients in close relationship to β-amyloid plaques, suggests a link of angiogenesis, VEGF upregulation and formation and deposition of β-amyloid. Due to the complex pharmacological profile of VEGF demonstrating angiogenic, neuroprotective, and neurogenic properties as well as high affinity
to β-amyloid, the project proposal stresses the hypothesis that VEGF up-regulated in AD, plays a role in the progression of the disease by affecting the processing of the β-amyloid precursor protein (APP).
To test for this hypothesis, intact cerebral cortical slices derived from transgenic Tg2576 mice that over express the Swedish mutation of human APP, are exposed to VEGF, and its effects on APP metabolism, β-amyloid production, α- and β-secretase expression and activity, secretion of soluble sAPPα, and sAPPβ is examined. To reveal cell-type specific effects including which VEGF receptor is involved, similar stimulation experiments are performed in primary neuronal and astroglial cell cultures derived from Tg2576 mouse brain.
To disclose whether the potential effects of VEGF on neuronal and astrocytic APP processing are mediated through activation of VEGF receptors, neuronal and astrocytic cells will be incubated with conditioned medium from hypoxia-exposed endothelial cells in the
presence of the non-selective VEGF receptor antagonist SU-5416 (50μM).
As VEGF has been shown to bind with high affinity to β-amyloid in vitro and to co-accumulate with β-amyloid plaques in brains of Alzheimer patients, the question should be answered whether VEGF may also affect or induce aggregation and fibrillogenesis of β-amyloid derived from Tg2576 mouse brain using a thioflavin-T binding assay.
The project proposal aims to reveal the role of VEGF in β-amyloidogenesis of AD, and whether the use of drugs targeting VEGF-mediated actions in the brain, represents a strategy to prevent or to treat AD.

Read more ...

 

References

RESEARCH ARTICLES
1. Bürger S, Noack M, Kirazov LP, Kirazov EP, Naydenov CL, Kouznetsova E, Yafai Y, Schliebs R. (2009)
Vascular endothelial growth factor (VEGF) affects processing of amyloid precursor protein and ß-amyloidogenesis in brain slice cultures derived from transgenic Tg2576 mouse brain. Int J Dev Neurosci, 27 (6):517-23

 MEETING ABSTRACTS
1. S. Bürger, M. Noack, E. Kouznetsova, Y. Yafai, L. Kirazov, E. Kirazov, R. Schliebs (2009)
Vascular endothelial growth factor (VEGF) affects processing of amyloid precursor protein and β-amyloidogenesis in brain slice cultures derived from transgenic Tg2576 mouse brain.
18th European Society for Neurochemistry (ESN), 4th Conference on Advances in Molecular Mechanisms of Neurological Disorders, Leipzig, July 11-14, 2009. Abstract in: J. Neurochem. 110, Suppl. 1, 2009, pp. 40-41

2. S. Bürger, M. Noack, E. Kouznetsova, Y. Yafai, L. Kirazov, E. Kirazov, R. Schliebs (2009)
Vascular endothelial growth factor (VEGF) affects processing of amyloid precursor protein and β-amyloidogenesis in brain slice cultures derived from transgenic Tg2576 mouse brain.
Saxon Biotechnology Symposium, May 26, 2009, in Leipzig. Abstract in: Saxon Biotechnology, Symposium 2009, Abstracts book (Eds. A.A. Robitzki, M. Blessing, T. Züchner, M. Brand, F. Stewart, A. Beyer, E. Schäffer), Leipzig 2009 (ISBN-Nr. 978-3-00-027884-6), p. 201.

3. S. Bürger, M. Noack, L. Kirazov, E. Kirazov, E. Kouznetsova, R. Schliebs (2008)
Effect of Vascular Endothelial Growth Factor (VEGF) on processing of amyloid precursor protein in brain slice and primary cell cultures derived from transgenic Tg2576 mice.
7th Leipzig Research Festival for Life Sciences, 12. Dezember 2008. Abstract in: 7th Leipzig, Research Festival for Life Sciences Abstract Book (J. Thiery, A. Beck-Sickinger, T. Arendt, Hrsg.), Leipzig (ISBN-Nr. 3-9810760-4-4), S. 11.