Focal adhesions regulate Aβ signaling and cell death in Alzheimer's disease

Alzheimer's disease (AD) is a neurodegenerative disorder that results front a loss of synaptic transmission and ultimately cell death. The presenting pathology of AD includes neuritic plaques composed of beta-amyloid peptide (A beta) and neurofibrillary tangles composed of hyperphosphorylated tau, with neuronal loss in specific brain regions. However, the mechanisms that induce neuronal cell loss remain elusive. Focal adhesion (FA) proteins assemble into intracellular complexes involved in integrin-mediated communication between the extracellular matrix and the actin cytoskeleton, regulating many cell physiological processes including the cell cycle. Interestingly, recent studies report that integrins bind to A beta fibrils, mediating A beta signal transmission from extracellular sites of A beta deposits into the cell and ultimately to the nucleus. In this review, we will discuss the A beta induced integrin/FA signaling pathways that mediate cell cycle activation and cell death. (c) 2007 Elsevier B.V. All rights reserved.