Visualizing interaction of proteins relevant to Alzheimer's disease in intact cells

Methods. 2008 Apr;44(4):299-303. doi: 10.1016/j.ymeth.2007.02.003.

Abstract

To understand normal function of memory studying models of pathological memory decline is essential. The most common form of dementia leading to memory decline is Alzheimer's disease (AD), which is characterized by the presence of neurofibrillary tangles and amyloid plaques in the affected brain regions. Altered production of amyloid beta (Abeta) through sequential cleavage of amyloid precursor protein (APP) by beta- and gamma-secretases seems to be a central event in the molecular pathogenesis of the disease. Thus, the study of the complex interplay of proteins that are involved in or modify Abeta production is very important to gain insight into the pathogenesis of AD. Here, we describe the use of Fluorescence lifetime imaging microscopy (FLIM), a Fluorescence resonance energy transfer (FRET)-based method, to visualize protein-protein-interaction in intact cells, which has proven to be a valuable method in AD research.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / diagnosis*
  • Amyloid beta-Protein Precursor / analysis*
  • Amyloid beta-Protein Precursor / genetics
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Cell Line, Tumor
  • Fluorescence Resonance Energy Transfer / methods*
  • Humans
  • Low Density Lipoprotein Receptor-Related Protein-1 / analysis*
  • Low Density Lipoprotein Receptor-Related Protein-1 / genetics
  • Low Density Lipoprotein Receptor-Related Protein-1 / metabolism
  • Mice
  • Microscopy, Fluorescence / methods
  • Phosphorylation
  • Protein Binding
  • Protein Conformation

Substances

  • Amyloid beta-Protein Precursor
  • Low Density Lipoprotein Receptor-Related Protein-1