Binding partners of Alzheimer's disease proteins: Are they physiologicallyrelevant?

Protein-protein interactions are a molecular basis for the structural and f unctional organization within cells. They are mediated by a growing number of protein modules that bind peptide targets. Alterations in binding affini ties can have serious consequences for some essential cellular processes. T he three proteins identified to have mutations in their corresponding genes leading to presenile Alzheimer dementia (AD)-the amyloid precursor protein (APP) and presenilin 1 and 2-all interact with other proteins. The nature and function of these interacting proteins may contribute to elucidating th e proper physiological functions of the AD proteins. APP-interacting protei ns are pointing toward a function of APP in cell adhesion and neurite outgr owth and signaling. Proteins interacting with the presenilins however are m ore diverse in nature linking presenilin function to regulation in differen t signaling pathways including Wnt and Notch but also in apoptosis and Ca2 homeostasis. Further research however is still needed to delineate the exa ct functional relevance of these interactions with respect to the physiolog ical functions of the AD proteins in particular and the contribution of the se proteins to AD pathogenesis in general. (C) 2000 Academic Press.