Regulation of Amyloidogenic secretases during apoptosis

Rudolph Tanzi, PhD
Massachusetts General Hospital (Charlestown, MA)
Year Awarded:
Grant Duration:
April 1, 2005 to March 31, 2007
Alzheimer's Disease
Award Amount:
Grant Reference ID:
Award Type:
Award Region:
US Northeastern

Regulation of Amyloidogenic secretases during apoptosis


Evidence is accumulating that stroke significantly increases the risk of AD representing either a precipitating or a triggering event. Extensive studies have shown that stroke or head trauma results in neuronal cell death by the activation of a cell death program termed apoptosis. Apoptosis is characterized by the activation of a family of protease called caspases. The pharmacological inhibition of caspases has been shown to reduce cell death. Dr. Tanzi's findings indicate that treatment of stroke and head trauma with caspase inhibitors might be useful not only to prevent neuronal cell death as a consequence of the acute events, but also to prevent the increase in Aβ production that contributes to AD pathogenesis. Dr. Tanzi's proposed experiments should not only increase our understanding of the regulation of the amyloidogenic secretases, but suggest novel therapeutic strategies for treating and preventing AD.


Koh, Y.H., von Arnim, C.A., Hyman, B.T., Tanzi, R.E. and Tesco, G. (2005) BACE is degraded via the lysosomal pathway. J Biol Chem. Sep 16;280(37):32499-504.  

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