Role of the Presenilin1mediated cleavage of Ephrin B proteins

Project Summary

Alzheimer's disease (AD) is a neurodegenerative disorder of the central nervous system (CNS). There are at least two forms of AD: the sporadic form, which inflicts most AD patients and usually occurs after the age of 65 or 70, and the familial form, which occurs at earlier stages and follows a more rapid progressive course than the sporadic disease. Familial AD (FAD) is caused by mutations in certain genes, including the amyloid precursor protein (APP) gene, presenilin-1 (PS1), and presenilin-2 (PS2). PS1 mutations are responsible for most cases of FAD. It was recently demonstrated that PS1 controls the γ-secretase-mediated cleavage of several type I transmembrane proteins like the APP, Notch, erbB4, CD44 and E-cadherin. EphrinB proteins are type I transmembrane proteins that are ligands for the ephrinB receptors (EphBs). Both proteins are expressed in the CNS and are also found at the neuronal synapses, where they play a very important role in the synaptic function affecting memory. The goal of this study is to investigate the role of PS1-dependent γ-secretase-like activity in the processing and function of ephrinB proteins.