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

Research reveals how the brain remembers fearful experiences

February 20, 2017

Understanding how the brain remembers can one day shed light on what went wrong when memory fails, such as it occurs in Alzheimer's disease. Researchers at Baylor College of Medicine and Rice University reveal for the first ...

Mercury in fish, seafood may be linked to higher risk of ALS

February 20, 2017

Eating fish and seafood with higher levels of mercury may be linked to a higher risk of amyotrophic lateral sclerosis (ALS), according to a preliminary study released today that will be presented at the American Academy of ...

Stem cell transplants may help some with multiple sclerosis

February 20, 2017

(HealthDay)—Stem cell transplants may halt the progression of aggressive multiple sclerosis (MS) in nearly half of those with the debilitating disease, but picking the right patients for the treatment is key, a new study ...

Hope for new treatment for Huntington's disease

February 20, 2017

Researchers working at Karolinska Institutet in Sweden and University of Southern Denmark have managed to produce short synthetic DNA analogues – oligonucleotides – that bind directly to the gene that is mutated in Huntington's ...

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.