Ludwig-Maximilians-Universität, Chair of Metabolic Biochemistry

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PhD topic

Identification of proteins binding to the 5`UTR of BACE1.

Thesis adviser(s)

Prof. Dr. Christian Haass, Dr. Sven Lammich


Alzheimer disease is characterized by neuronal loss, astrogliosis, amyloid plaques and neurofibrillary tangles in the brain. Plaques mainly consist of the 40 or 42 amino acid long amyloid-beta peptide (Aβ) which is generated from the amyloid precursor protein (APP) by β- and γ-secretase. In contrast α-secretase prevents the formation of Aβ by cleaving APP within the Aβ domain.

We and two other research groups could independently show that the 5`UTR of BACE1 inhibits the translation of the BACE1 mRNA but not the transcription of BACE1 (Lammich et al., 2004; Rogers et al., 2004; Tonelli et al.,2004). A possible explanation for the observed 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.
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 hypothesize that these binding proteins might regulate translation of BACE1. Characterization of the expression of BACE1 will allow a better knowledge about the role of BACE1 in AD as well as in healthy people. This might open completely new strategies for drug development.


The PhD project is funded by the Hans and Ilse Breuer Stiftung.