New target for Alzheimer's disease identified

May 07, 2008

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, A peptides—in 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 neuronal damage, the scientists found that the enkephalin levels were also affected. Furthermore, as levels of the enkephalins increased, the ability of mice to complete behavioral tests declined. Compounds that blocked opioid receptors, through which enkaphalins exert their effects, reduced cognitive deficits. AD patients also showed increased levels of enkephalins in brain regions affected by the disease.

“Our results indicate that the high levels of enkephalins may contribute to cognitive impairments in hAPP mice and maybe also in AD patients,” said Dr. Mucke. “Although these are early results, they are encouraging and may lead the way to a new AD therapy based on limiting enkephalin production or signaling.”

Source: Gladstone Institutes

Explore further: Missing protein restored in patients with muscular dystrophy

add to favorites email to friend print save as pdf

Related Stories

Infant pain, adult repercussions

Sep 25, 2009

Scientists at Georgia State University have uncovered the mechanisms of how pain in infancy alters how the brain processes pain in adulthood.

Gene therapy for chronic pain gets first test in people

Sep 15, 2008

This week, University of Michigan scientists will begin a phase 1 clinical trial for the treatment of cancer-related pain, using a novel gene transfer vector injected into the skin to deliver a pain-relieving ...

Recommended for you

Student seeks to improve pneumonia vaccines

Aug 20, 2014

Almost a million Americans fall ill with pneumonia each year. Nearly half of these cases require hospitalization, and 5-7 percent are fatal. Current vaccines provide protection against some strains of the ...

Seabed solution for cold sores

Aug 20, 2014

The blue blood of abalone, a seabed delicacy could be used to combat common cold sores and related herpes virus following breakthrough research at the University of Sydney.

Better living through mitochondrial derived vesicles

Aug 19, 2014

(Medical Xpress)—As principal transformers of bacteria, organelles, synapses, and cells, vesicles might be said to be the stuff of life. One need look no further than the rapid rise to prominence of The ...

Zebrafish help to unravel Alzheimer's disease

Aug 19, 2014

New fundamental knowledge about the regulation of stem cells in the nerve tissue of zebrafish embryos results in surprising insights into neurodegenerative disease processes in the human brain. A new study by scientists at ...

User comments : 0