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

Document Type

Article

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder that results from a loss of synaptic transmission and ultimately cell death. The presenting pathology of AD includes neuritic plaques composed of beta-amyloid peptide (Aβ) 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 Aβ fibrils, mediating Aβ signal transmission from extracellular sites of Aβ deposits into the cell and ultimately to the nucleus. In this review, we will discuss the Aβ induced integrin/FA signaling pathways that mediate cell cycle activation and cell death. © 2007 Elsevier B.V. All rights reserved.

Keywords

Alzheimer's disease, Cell cycle, Cyclin D1, FAK, Integrin, Paxillin

Publication Date

4-1-2007

Publication Title

Biochimica et Biophysica Acta - Molecular Basis of Disease

ISSN

09254439

Volume

1772

Issue

4

First Page

438

Last Page

445

PubMed ID

17215111

Digital Object Identifier (DOI)

10.1016/j.bbadis.2006.11.007

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