UC San Diego Logo Recently we had reported that naturally occurring plant alkaloids can slow down Alzheimer’s disease. And now researchers from the University of California, San Diego, the Medical University of South Carolina and American Life Science Pharmaceuticals of San Diego claim that oral administration of a cysteine protease inhibitor, E64d decreases the build-up of β-amyloid (Aβ) in the brains of animal models for Alzheimer’s disease. It also appears to produce a significant improvement in memory deficit.

The development of memory loss and amyloid plaque possibly correlates with elevation in Aβ levels within the brain. Apparently, Aβ peptides are ‘cut’ out from a larger protein known as amyloid precursor protein (APP) by an enzymatic ‘scissor’ called β-secretase, and aggregate to form plaques in the brain regions responsible for memory. E64d allegedly reduces Aβ by inhibiting the β-secretase ‘scissors’ from ‘cutting’ the APP chain into smaller toxic Aβ peptides. During the research, the compound was found to seemingly boost the activity of a protease called BACE1.

“The study indicates Cathepsin B as a new target for therapeutic inhibition of Aβ production and subsequent improved memory function. This is an important finding because we show that β-secretase inhibition can occur with Cathepsin B inhibition and without BACE1 inhibition,” explained lead investigator Vivian Y. H. Hook, PhD, professor of neurosciences, pharmacology and medicine at the UCSD School of Medicine.

E64d, on the other hand, is presumed to lower brain Aβ by inhibiting the β-secretase activity of another protease, Cathepsin B. Both old and young transgenic Alzheimer’s disease mice were thoroughly scrutinized. Improvement in memory loss was reported by the two groups. In young mice, feeding E64d purportedly restricted the development of memory loss. Among old mice with memory loss, it supposedly enhanced memory.

The research appears online and will be published in the September 6 issue of the Journal of Alzheimer’s Disease.