Über die Interaktionen des zellulären Prion-Proteins (PrPc) mit relevanten Proteinen der Alzheimer Erkrankung

Über die Interaktionen des zellulären Prion-Proteins (PrPc) mit relevanten Proteinen der Alzheimer Erkrankung

The interaktion of the cellular prion protein (PrPc) with relevant proteins of Alzheimer's disease

Katharina Maibach-Wulf

Doctoral thesis

Date of Examination: 2014-07-15

Date of issue: 2014-07-08

Advisor: Zerr, Inga Prof. Dr.

Referee: Wirths, Oliver PD Dr.

Referee: Schu, Peter Prof. Dr.

Persistent Address: http://hdl.handle.net/11858/00-1735-0000-0022-5F0C-F

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Abstract

English

Previous studies indicate an important role for the cellular prion Protein (PrPc) in the development of Alzheimer's disease pathology. In the present study the interaction of PrPc with Alzheimer relevant proteins such as APP, BACE, tau and phosphorylated tau was identified. In addition, this study shows that PrPc reduces APP cleavage, leading to decreased Levels of APP-beta, APP-alpha and A-beta 40 without changing the protein expression of APP or BACE. This results could be shown in a cell model using HEK 293 and SHSY5Y cells and additionally in a mouse model using a PrPc knockout (Prnp0/0) mouse line.

Keywords: Alzheimer's disease, amyloid, beta-secretase, cellular prion protein, tau, ptau