Alzheimer's 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 today's 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 Alzheimer's 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 Alzheimer's 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 AD-human amyloid precursor protein (hAPP) and its cleavage product, AƒÒ peptides-in neurons and exhibit several characteristics of AD.