Biomedical Engineering Reference
In-Depth Information
CHAPTER 6
Discovery of the Cysteine
Protease Cathepsin B as a Drug
Target for Alzheimer's Disease
VIVIAN HOOK,*
a
MARK KINDY
b
AND
GREGORY HOOK
c
a
Skaggs School of Pharmacy and Pharmaceutical Sciences, Departments of
Neurosciences, Pharmacology, and Medicine, University of California,
La Jolla, CA 92093, USA;
b
Department of Neurosciences, Medical
University of South Carolina and the Ralph H. Johnson VA
Medical Center, Charleston, SC 29425, USA;
c
American Life
Science Pharmaceuticals, Inc., San Diego, CA 92109, USA
6.1 Introduction: Alzheimer's Disease and b-Amyloid
Alzheimer's disease (AD) results in severe memory loss resulting from age-
related neurodegeneration in the brain, caused in large part by accumulation of
neurotoxic b-amyloid (Ab) peptides. The majority of AD patients are aicted
with sporadic AD that is not linked to genetic mutations.
1,2
A smaller portion
of AD patients possess familial forms of AD with inherited genetic mutations,
especially mutations of APP and presenilins that result in increased Ab pro-
duction and memory deficit when overexpressed in transgenic mouse models of
AD.
3-5
Development of effective therapeutic agents to improve memory in AD
is essential for the increasing numbers of AD patients who are becoming
aicted as the aged population grows.
A logical therapeutic approach for AD is to develop drugs which reduce the
production of brain Ab peptides because their accumulation has been
