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

January 25, 2012

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

Study finds graspable objects grab attention more than images of objects do

December 15, 2017
Does having the potential to act upon an object have a unique influence on behavior and brain responses to the object? That is the question Jacqueline Snow, assistant professor of psychology at the University of Nevada, Reno, ...

Little understood cell helps mice see color

December 14, 2017
Researchers at the University of Colorado Anschutz Medical Campus have discovered that color vision in mice is far more complex than originally thought, opening the door to experiments that could potentially lead to new treatments ...

Scientists chart how brain signals connect to neurons

December 14, 2017
Scientists at Johns Hopkins have used supercomputers to create an atomic scale map that tracks how the signaling chemical glutamate binds to a neuron in the brain. The findings, say the scientists, shed light on the dynamic ...

Activating MSc glutamatergic neurons found to cause mice to eat less

December 13, 2017
(Medical Xpress)—A trio of researchers working at the State University of New York has found that artificially stimulating neurons that exist in the medial septal complex in mouse brains caused test mice to eat less. In ...

Gene mutation causes low sensitivity to pain

December 13, 2017
A UCL-led research team has identified a rare mutation that causes one family to have unusually low sensitivity to pain.

Scientists discover blood sample detection method for multiple sclerosis

December 13, 2017
A method for quickly detecting signs of multiple sclerosis has been developed by a University of Huddersfield research team.

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.