In vitro study of interaction of 17ß-hydroxysteroid dehydrogenase type 10 and cyclophilin D and its potential implications for Alzheimer's disease.

ABSTRACT

In early stages of Alzheimer's disease (AD), amyloid-ß (Aß) accumulates in neuronal mitochondria where it interacts with a number of biomolecules including 17beta-hydroxysteroide dehydrogenase 10 (17ß-HSD10) and cyclophilin D (cypD). It has been hypothesized that 17ß-HSD10 interacts with cypD preventing it from opening mitochondrial permeability transition pores and that its regulation during AD may be affected by the accumulation of Aß. In this work, we demonstrate for the first time that 17ß-HSD10 and cypD form a stable complex in vitro. Furthermore, we show that factors, such as pH, ionic environment and the presence of Aß, affect the ability of 17ß-HSD10 to bind cypD. We demonstrate that K+ and Mg2+ ions present at low levels may facilitate this binding. We also show that different fragments of Aß (Aß1-40 and Aß1-42) affect the interaction between 17ß-HSD10 and cypD differently and that Aß1-42 (in contrast to Aß1-40) is capable of simultaneously binding both 17ß-HSD10 and cypD in a tri-complex.