Binding partners of Alzheimer's disease proteins: are they physiologically relevant?
Protein-protein interactions are a molecular basis for the structural and functional organization within cells. They are mediated by a growing number of protein modules that bind peptide targets. Alterations in binding affinities can have serious consequences for some essential cellular processes. The 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 the proper physiological functions of the AD proteins. APP-interacting proteins are pointing toward a function of APP in cell adhesion and neurite outgrowth and signaling. Proteins interacting with the presenilins however are more diverse in nature linking presenilin function to regulation in different signaling pathways including Wnt and Notch but also in apoptosis and Ca(2+) homeostasis. Further research however is still needed to delineate the exact functional relevance of these interactions with respect to the physiological functions of the AD proteins in particular and the contribution of these proteins to AD pathogenesis in general.
Van Gassen
G
G
Molecular Genetics Laboratory, University of Antwerp (UIA), Antwerpen, Belgium.
Annaert
W
W
Van Broeckhoven
C
C
D000544:Alzheimer Disease / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D017209:Apoptosis / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism* / Q000502:physiology; D016501:Neurites / Q000502:physiology; D053764:Presenilin-1; D053766:Presenilin-2; D051880:Receptors, Notch; D015398:Signal Transduction / Q000502:physiology
D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2; D051880:Receptors, Notch