Identification of BAmyloid Precursor Protein Ligands

Luciano D'Adamio, MD, PhD
Albert Einstein College of Medicine (Bronx, NY)
Year Awarded:
2003
Grant Duration:
April 1, 2003 to March 31, 2005
Disease:
Alzheimer's Disease
Award Amount:
$200,000
Grant Reference ID:
A2003076
Award Type:
Standard
Award Region:
US Northeastern

Identification of BAmyloid Precursor Protein Ligands

Details


Alzheimer's disease is considered by some to be caused by brain deposits of amyloid beta (Aß) protein plaques. These plaques are formed by the accumulation of a toxic molecule called Aß peptides. This peptide originates from the cleavage of amyloid precursor protein (APP) by proteolytic enzymes called secretases. Understanding the factor(s) that are instrumental in initiating the APP cleavage cascade would be important for the development of drugs to prevent and treat this disease. An APP ligand that can regulate the processing of APP could be a major therapeutic target. It is hoped that modulators of this interaction, once discovered, might be used to create safe and specific Alzheimers disease drugs with limited toxic side effects.

Publications

Matsuda, S., Giliberto, L., Matsuda, Y., Davies, P., McGowan, E., Ghiso, J., Frangione, B., and D'Adamio, L. (2005) The familial dementia BR12 gene binds the Alzheimer's gene amyloid-beta precursor protein and inhibits amyloid-beta production. J Biol Chem. 280(32):28912-28916.  

Matsuda S, Giliberto L, Matsuda Y, McGowan EM, D'Adamio L. BRI2 inhibits amyloid beta-peptide precursor protein processing by interfering with the docking of secretases to the substrate. J Neurosci. 2008 Aug 27;28(35):8668-76.  

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