ABSTRACT

One of the most prominent neuropathologic features of Alzheimer’s disease is widespread cerebral deposition of a 39-43-amino acid peptide called the amyloid-β peptide (Aβ) in the form of amyloid fibrils.1 It is generally believed that Aβ plays a central role in the progressive neurodegeneration observed in Alzheimer’s disease (AD). Aβ is generated from a larger protein called the Aβ precursor protein (APP) by a group of enzymes collectively identified as secretases. Specifically, APP is proteolytically cleaved at specific amino acids by three enzymes, α-, β-and γ-secretase, to different protein fragments, including the toxic Aβ and other C-terminal fragments that are implicated in the pathogenesis of AD.1,2 Our laboratories are engaged in studying various classes of agents that can reduce APP expression, as this is the precursor to all the Aβ toxic fragments. Over the years we have tested the effects of several clinically useful drugs/compounds on the APP metabolic pathways.2