Axonal transport of APP and the spatial regulation of APP cleavage and function in neuronal cells

SILKE BRUNHOLZ; SANGRAM SISODIA; ALFREDO LORENZO; CAROLE DEYTS; STEFAN KINS; GERARDO MORFINI

SPRINGER

Año: 2011

ver two decades have passed since the original discovery of amyloid precursor protein (APP). While physiological function(s) of APP still remain a matter of debate, consensus exists that the proteolytic processing of this protein represents a critical event in the life of neurons and that abnormalities in this process are instrumental in Alzheimer?s disease (AD) pathogenesis. Specific molecular components involved in APP proteolysis have been identified, and their enzymatic activities characterized in great detail. As specific proteolytic fragments of APP are identified and novel physiological effects for these fragments are revealed, more obvious becomes our need to understand the spatial organization of APP proteolysis. Valuable insights on this process have been obtained through the study of non-neuronal cells. However, much less is known about the topology of APP processing in neuronal cells, which are characterized by their remarkably complex cellular architectur