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New target for Alzheimer's disease identified
Date:5/7/2008

SAN FRANCISCO, CA May 7, 2008 ---Alzheimers disease (AD) is an incurable disease that is increasing in prevalence and will increase even more rapidly as the Baby Boom generation enters the age of highest risk. The available AD drugs are only partially effective in some patients. New strategies are urgently needed.

In a new study, published in todays Journal of Neuroscience, researchers in the laboratory of Lennart Mucke, MD, director of the Gladstone Institute of Neurological Disease (GIND), have determined in mouse models that modulating the activity of enkephalin peptides in the brain might reduce the cognitive deficits seen in Alzheimers disease.

Enkephalins are part of the endogenous opioid system, which modulates learning and memory and other brain functions. They are produced by several different cell types in the brain, particularly in areas affected by AD. Enkephalins are derived by enzymatic cleavage from a precursor protein, preproenkephalin, and stored in vesicles. Upon stimulation, enkephalins are released with neurotransmitters, such as glutamate.

The enkephalin pathway is an intriguing candidate for us because it is involved in many functions that are affected by Alzheimers and other neurodegenerative diseases, said Dr. Mucke. We were not sure, though, whether it contributed causally to the disease or acts as a compensatory mechanism.

To better understand the activities of the enkephalins in AD, the Mucke team examined their functions in a transgenic mouse model of AD. These mice express two proteins associated with ADhuman amyloid precursor protein (hAPP) and its cleavage product, A peptidesin neurons and exhibit several characteristics of AD.

The team found increased levels of preproenkephalin mRNA and of enkephalin in brain regions important for memory that are affected in early stages of AD.

When they genetically manipulated the mice to make them more or less susceptible to neur
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Contact: Valerie Tucker
vtucker@gladstone.ucsf.edu
415-734-2019
Gladstone Institutes
Source:Eurekalert

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