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

Biochim Biophys Acta. 2007 Apr;1772(4):438-45. doi: 10.1016/j.bbadis.2006.11.007. Epub 2006 Nov 30.

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 (Abeta) 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 Abeta fibrils, mediating Abeta signal transmission from extracellular sites of Abeta deposits into the cell and ultimately to the nucleus. In this review, we will discuss the Abeta induced integrin/FA signaling pathways that mediate cell cycle activation and cell death.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Alzheimer Disease / pathology*
  • Amyloid beta-Peptides / physiology*
  • Cell Adhesion / physiology*
  • Cell Cycle
  • Cell Death
  • Cell Survival
  • Humans
  • Integrins / physiology
  • Neurons / cytology
  • Neurons / pathology
  • Signal Transduction
  • Transcription, Genetic

Substances

  • Amyloid beta-Peptides
  • Integrins