Interdisciplinary Bio Central
Review (General)

The Roles of GxxxG Motif and Gamma-Secretase Components in APP Processing
Jungsu Kim1,*
1Department of Neurology, Washington University Medical School, St. Louis, MO 63110, USA
*Corresponding author
  Received : December 30, 2009
  Accepted : December 31, 2009
  Published : December 30, 2009
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Main text PDF(2619KB)
   (Print version)

Alzheimer's disease (AD) is the leading cause of dementia in the elderly. Although the pathological features of AD, including excessive amyloid deposits, neurofibrillary tangles, neuroinflammatory responses, and progressive neuronal loss, have been relatively well-characterized, the pathogenic mechanisms underlying neurodegeneration and cognitive decline in AD remain unclear. Recent findings suggest that GxxxG glycine zipper motifs in amyloid-β precursor protein (APP) and Aβ peptide play critical roles in APP dimerization as well as Aβ production and fibrillogenesis. Given the fact that the glycine zipper motif is also found in α-synuclein and prion protein, already implicated in other neurodegenerative diseases, further understanding of this motif might provide novel therapeutic targets for protein misfolding disorders. Another research area of growing interest is γ-secretase. Although the process of intramembranous endoproteolysis was initially believed to be biochemically unfeasible to happen due to the hydrophobic environment of membranes, subsequent studies convincingly demonstrated that regulated intramembrane proteolysis does occur and it plays a critical role in cellular signaling and inflammatory response. Recent studies have identified more γ-secretase substrates and provided conflicting findings on the roles of γ-secretase components. Additional investigations into γ-secretase function may enhance our understanding of AD etiology and lead to the development of safer and more effective therapeutics.

Keyword: γ-secretase, GxxxG glycine zipper motifs, , Alzheimer disease
IBC   ISSN : 2005-8543   Contact IBC