ABSTRACT
Alzheimer’s Disease ...............................................................................329 19.3 β-Amyloid Peptide is Generated by Proteolytic Processing of the
Amyloid Precursor Protein.....................................................................329 19.4 β-Amyloid Production and Secretion in the Major Regulated
Secretory Pathway of Neurons ...............................................................330 19.5 Regulated Cosecretion of β-Amyloid with Neurotransmitters
from Neuronal Chromaffin Cells in Primary Culture ............................330 19.6 Chromaffin Vesicles as Regulated Secretory Vesicles for
Identification of β-Secretase ..................................................................332
19.7 Cysteine Proteases for β-Secretase Activity in the Regulated Secretory Pathway of Neurons .............................................................333
19.8 Kinetic Studies of the Cysteine β-Secretases Demonstrate their Preference for Cleavage of the Wild-Type β-Secretase Site, Rather than the Swedish Mutant β-Secretase Site ...............................336
19.9 BACE 1 in the Minor Constitutive Secretory Pathway for Basal Secretion of β-Amyloid..............................................................337
19.10 Unifying Hypothesis for Distinct Proteases in the Regulated Compared to the Constitutive Secretory Pathways for β-Amyloid Production and Secretion: Strategies for Drug Inhibition of β-Secretase to Treat Alzheimer’s Disease............................................339
Acknowledgments .............................................................................................339 References .........................................................................................................340
Alzheimer’s disease (AD) is a progressive, long-term, debilitating mental disorder that causes loss of memory and cognitive functions. Over 4 million Americans are afflicted with AD and the disease costs the US economy billions of dollars every year. Currently, there is no effective treatment for the disease, and therefore, there is an urgent need for effective therapeutic agents to ameliorate the detrimental conditions of AD.
