BioCentury
ARTICLE | Tools & Techniques

Chasing APP's tail

July 9, 2001 7:00 AM UTC

Companies such as Bristol-Myers Squibb Co. are targeting gamma secretase for Alzheimer's disease. However, an article last week in Science complicates this approach by suggesting that one of the secretase's cleavage products might be involved in transcriptional regulation. Thus, although the inhibition of gamma secretase might decrease the production of the plaque-forming amyloid beta, such activity potentially could interfere with transcriptional regulation, resulting in unexpected side effects.

Researchers from the University of Texas Southwestern Medical Center in Dallas reported that the intracellular fragment of amyloid precursor protein (APP) resulting from gamma secretase cleavage forms a complex with nuclear adaptor protein Fe65 and the histone acetyltransferase Tip60. The complex was found to stimulate transcription, suggesting that the cytoplasmic tail of APP may function in gene expression...