Protein in the brain could be a key target in controlling Alzheimer's

January 25, 2012, Temple University

A protein recently discovered in the brain could play a key role in regulating the creation of amyloid beta, the major component of plaques implicated in the development of Alzheimer's disease, according to researchers at Temple University's School of Medicine.

A group led by Domenico Pratico, professor of and microbiology and immunology at Temple, discovered the presence of the , called 12/15-Lipoxygenase, in the brain three years ago.

"We found this protein to be very active in the brains of people who have Alzheimer's disease," said Pratico. "But three years ago, we didn't know the role it played in the development of the disease."

Following two years of study, the Temple researchers have found that the protein is at the top of a and controls a biochemical that begins the development of Alzheimer's. They have published their findings, "Transcriptional Regulation of ßsecretase-1 by 12/15 Lipoxygenase Results in Enhanced Amyloidogenesis and Cognitive Impairments," in the journal Annals of Neurology.

Pratico said that their research has shown that 12/15-Lipoxygenase controls Beta secretase (BACE-1), an enzyme that is key to the development of amyloid plaques in Alzheimer's patients.

"For reasons we don't yet know, in some people, 12/15-Lipoxygenase starts to work too much," he said. "By working too much, it sends the wrong message to the Beta secretase, which in turn starts to produce more amyloid Beta. This initially results in cognitive impairment, memory impairment and, later, an increase of amyloid ."

BACE-1 has long been a biological target for researchers seeking to create a drug against , said Pratico. But because little has been known about how it functions, they have been unsuccessful developing a molecule that could reach the brain and block it.

"We now know much better how Beta secretase works because we have found that the 12/15-Lipoxygenase protein is a controller of BACE functions," he said. "You don't need to target the Beta secretase directly because the 12/15-Lipoxygenase is really the system in the brain that tells BACE to work more or work less."

Pratico said that they have validated 12/15-Lipoxygenase as a target for a potential Alzheimer drug or therapy.

"By modulating BACE levels and activity through controlling the 12/15-Lipoxygenase, we can potentially improve the cognitive part of the phenotype of the disease, and prevent the accumulation of amyloid beta inside the neurons, which will eventually translate into less of those plaques," he said. "This is a totally new mechanism for controlling BACE."

Pratico said his group has looked at an experimental compound that blocks 12/15-Lipoxygenase function as a potential therapy to inhibit BACE function in the brain. In their lab, using animal models, they saw the drug's ability to restore some cognitive function, as well as improve learning and memory ability.

"There is an opportunity here to study this molecule and develop an even stronger molecule to target 12/15-Lipoxygenase function in the ," he said.

Explore further: Road block as a new strategy for the treatment of Alzheimer's

Related Stories

Road block as a new strategy for the treatment of Alzheimer's

August 22, 2011
Blocking a transport pathway through the brain cells offers new prospects to prevent the development of Alzheimer's. Wim Annaert and colleagues of VIB and K.U. Leuven discovered that two main agents involved in the inception ...

Recommended for you

A peek into the interplay between sleep and wakefulness

July 20, 2018
Sleep is an autonomic process and is not always under our direct, voluntary control. Awake or asleep, we are basically under the regulation of two biological processes: sleep homeostasis, commonly known as 'sleep pressure', ...

Paralyzed mice with spinal cord injury made to walk again

July 19, 2018
Most people with spinal cord injury are paralyzed from the injury site down, even when the cord isn't completely severed. Why don't the spared portions of the spinal cord keep working? Researchers at Boston Children's Hospital ...

Neural inflammation plays critical role in stress-induced depression

July 19, 2018
A group of Japanese researchers has discovered that neural inflammation caused by the innate immune system plays an unexpectedly important role in stress-induced depression. This insight could potentially lead to the development ...

Scientists uncover the role of a protein in production and survival of myelin-forming cells

July 19, 2018
The nervous system is a complex organ that relies on a variety of biological players to ensure daily function of the human body. Myelin—a membrane produced by specialized glial cells—plays a critical role in protecting ...

Understanding the neuroscience of binge drinking

July 19, 2018
A new study from researchers at Columbia University Irving Medical Center found that binge drinking impairs working memory in the adolescent brain. The study, in mice, explains why teenagers who binge drink are 15 times more ...

Neurons can carry more than one signal at a time

July 18, 2018
Back in the early days of telecommunications, engineers devised a clever way to send multiple telephone calls through a single wire at the same time. Called time-division multiplexing, this technique rapidly switches between ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.