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Alzheimer's Disease Research - Current Award

Photo Pending

Tae-Wan Kim, Ph.D.

Columbia University
New York, NY

Title: Modulation of BACE1 by a Novel Sorting Nexin
Non-Technical Title: BACE1 Trafficking and Alzheimer's Disease

Duration: April 1, 2008 - March 31, 2011
Award Type: Standard
Award Amount: $265,000


Summary:

This study will investigate the mechanism underlying the regulation of BACE1 trafficking and beta-amyloid generation in neurons by a novel sorting nexin. Gaining insight into these cellular mechanisms will lead to development of novel therapeutic approaches for preventing or treating AD.

Details:

Aberrant trafficking of Alzheimer's disease (AD)-associated molecules, such as beta-amyloid precursor protein (APP) and beta-site APP-cleaving enzyme 1 (BACE1), has been extensively implicated in the neuropathogenesis of AD. BACE1 mediates the first of two cleavage events of APP to yield amyloid beta-peptide (A-beta). Recent studies suggest that aberrant regulation of molecular components of the endosome and trans-Golgi network (TGN) may contribute to the enhanced A-beta levels associated with AD. We discovered that a novel sorting 'nexin', a member of the family of trafficking proteins that bind phospholipids, binds BACE1 and regulates the cleavage of APP. Our proposed studies will investigate the mechanism underlying the regulation of BACE1 trafficking and beta-amyloid generation in neurons by this novel sorting nexin. Gaining insight into these cellular mechanisms will lead to development of novel therapeutic approaches for preventing or treating AD.