Sonja Zilow

Spenden & Helfen

Curriculum vitae

Name Sonja Zilow
Place of birth Heidelberg, Germany
Date of birth 30.12.1980
since 2005 PhD under Prof. Haass at the Adolf- Butenandt- Institute,
Ludwig-Maximilians University, Munich
2005 Masterarbeit: “Analysis of the role of Rer1 in ER-retention of non-assembled gamma-secretase complex components” am Adolf- Butenandt- Institut, Ludwig-Maximilians Universität, München (AG: Prof. Haass, Dr. Kaether)
2004/2005 Biotechnology, Master of Science at the University of applied science, Mannheim
2000-2004 Biotechnology, Bachelor of Science with Honours at the University of Applied Science, Mannheim

Project description

Identification of proteins binding to the 5`untranslated region of the b-secretase

Alzheimer`s disease (AD) is the most common form of dementia among older people. It is a progressive, neurodegenerative disease characterized by neuronal loss, astrogliosis, amyloid plaques and neurofibrillary tangles in the brain.

Plaques mainly consist of the 40-42 amino acid long amyloid-b peptide (Ab) which is derived through proteolysis of the b-amyloid precursor protein (APP) by b- and g-secretase. In contrast a-secretase prevents the formation of Ab by cleaving APP within the Ab domain.

Analysis of brains of AD patients showed that BACE1 protein expression in comparison to brains of patients with no AD is increased by a factor of 2.7. This increase in BACE1 protein expression is not based on higher mRNA levels. Therefore it seems that BACE1 is regulated through post-transcriptionally mechanisms such as translational control or reduced degradation. Recently, it was shown that the 5`untranslated region (5`UTR) of BACE1 inhibits the translation of the BACE1 mRNA but not the transcription of BACE1. A possible explanation for the ob- served effects of the 5`UTR of BACE1 on the protein expression is that proteins which bind to the 5`UTR may be responsible for the repression of BACE1 translation.

Since BACE1 expression plays a crucial role in the pathogenesis of AD, the aim of the current project is to understand how the expression of BACE1 is regulated in more detail. Therefore the goal of my PhD thesis is to identify proteins binding to the 5`UTR of BACE1 since we hypo- thesize that these binding proteins might regulate translation of BACE1.

The identification and characterization of these proteins should allow a better understanding of the regulation of BACE1 expression in AD as well as in healthy people. This can lead to the identification of signal transduction pathways that might play a role for the increased BACE1 expression in AD. The better understanding of the BACE1 expression might open completely new strategies for drug development.