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New drug target improves memory in mouse model of Alzheimer's disease
Date:3/7/2012

Researchers at the University of California, San Diego, the Medical University of South Carolina, the University of Cincinnati, and American Life Science Pharmaceuticals of San Diego have validated the protease cathepsin B (CatB) as a target for improving memory deficits and reducing the pathology of Alzheimer's disease (AD) in an animal model representative of most AD patients. The study has been published in the online edition of the Journal of Alzheimer's Disease.

According to investigator Vivian Y. H. Hook, PhD, professor of the UCSD Skaggs School of Pharmacy and Pharmaceutical Sciences and professor of neurosciences, pharmacology and medicine at the UCSD School of Medicine, the study is important because it could lead to new therapeutics that improve the memory deficits of AD.

Abnormal accumulation of brain amyloid-β peptides (Aβ) is thought to cause the memory loss and amyloid plaque pathology of AD. Aβ peptides are "cut" out from a larger protein called the amyloid precursor protein (APP) by an enzymatic "scissor" called β-secretase, and aggregate to form plaques in the brain regions responsible for memory. Inhibiting the β-secretase "scissors" from "cutting" the APP with a drug would reduce brain Aβ levels and thereby improve memory deficits and reduce amyloid plaque pathology. The vast majority of AD patients have wild-type (WT) β-secretase activity and thus the WT β-secretase has been a target of great interest for a long time.

Another protease, BACE1, has long been thought to be the -secretase involved in AD pathology, because deleting that gene from animal models reduces brain A and plaque pathology. However, deleting the BACE1 gene was reported to make memory deficits worse in a transgenic model having WT β-secretase activity.

Hook and colleagues set off to find a WT β-secretase target, which improves memory deficits while reducing amy
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Contact: Debra Kain
ddkain@ucsd.edu
619-543-6163
University of California - San Diego
Source:Eurekalert

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