Effects of X11 amyloid precursor protein interaction

Project: Research project

Project Details

Description

DESCRIPTION (provided by applicant):
Alzheimer's disease affects four million people in the US, a number that is
expected to triple in the next fifty years. Understanding the basic mechanisms
that lead to AD is essential for the development of effective treatments. The
goal of this research is to determine the consequences of X11 alpha interaction
with APP on its trafficking and processing. We hypothesize that X11 alpha
binding to the carboxy terminus of APP reduces Abeta secretion by blocking APP
endocytosis and gamma secretase mediated cleavage and that lin2 binding to the
amino terminal domain of X11 alpha will abrogate this effect on APP in
transfected cells. We will determine if X11 alpha alters Abeta production by
impairing endocytosis of APP. Using single missense mutations in the YENPTY
internalization sequence of APP, we will examine whether endocytosis can be
dissected away from X11 alpha mediated effects on APP processing. Second we
will determine if X11 alpha interaction with APP inhibits
presenilin1/gamma-secretase mediated increases in Abeta 42 generation. Third,
we will determine if binding of lin2/CASK to the amino terminus of X11 alpha
will block the ability of X11 alpha to interact with APP and alter its
processing.
StatusFinished
Effective start/end date6/1/022/13/04

Funding

  • National Institute of Neurological Disorders and Stroke: $27,371.00
  • National Institute of Neurological Disorders and Stroke: $23,132.00

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