Researchers at the Gladstone Institute of Neurological Disease (GIND) have identified a potential target for Alzheimer's disease.
They 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 (AD).
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 Lennart Mucke, MD, director of the Gladstone Institute of Neurological Disease (GIND),
"We were not sure, though, whether it contributed causally to the disease or acts as a compensatory mechanism," Mucke added.
In order to have a better understanding of the activities of the enkephalins in AD, researchers examined their functions in a transgenic mouse model of AD.
These mice express two proteins linked to AD - human amyloid precursor protein (hAPP) and its cleavage product, Ab peptides-in neurons and exhibit several characteristics of AD.
Researchers found increased levels of preproenkephalin mRNA and of enkephalin in brain regions important for memory that are affected in early stages of AD.