12/15-Lipoxygenase Protein May Help Control Alzheimer's

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Main Category: Alzheimer's / Dementia
Article Date: 27 Jan 2012 - 11:00 PST

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Researchers at the Temple University's School of Medicine recently identified a protein in the brain that could have a major role in regulating the creation of amyloid beta, the major component of plaques implicated in the development of Alzheimer's disease.

Three years ago, the presence of the protein, called 12/15-Lipoxygenase, was detected in the brain by leading researcher Domenico Pratico, professor of pharmacology and microbiology and immunology at Temple, who said:

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



After two years of study, their findings of "Transcriptional Regulation of ßsecretase-1 by 12/15 Lipoxygenase Results in Enhanced Amyloidogenesis and Cognitive Impairments," were published in Annals of Neurology, revealing that the protein is located at the top of a pathway, controlling a biochemical chain reaction that initiates the development of Alzheimer's.

Their research demonstrated that 12/15-Lipoxygenase regulates Beta secretase (BACE-1), an enzyme that is vital in the development of amyloid plaques in Alzheimer's patients. 



Pratico explains:

"For reasons we don't yet know, in some people, 12/15-Lipoxygenase starts to work too much. 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 plaque."



Researchers have long focused on BACE-1 as a biological target in their quest of developing a drug against Alzheimer's disease, but given that little has been known about how it works, they remained unsuccessful in developing a molecule able to reach the brain and block it, says Pratico, adding, 

"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. 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."

He declares that 12/15-Lipoxygenase has been confirmed as a target for a potential Alzheimer drug or therapy and says:



"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. This is a totally new mechanism for controlling BACE."



Pratico's team has found an experimental compound that blocks 12/15-Lipoxygenase function as a potential therapy to block BACE function in the brain. They observed in animal models in their lab that the drug has the ability to restore some cognitive function and improve learning and memory ability.

Pratico concludes:



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

Written By Petra Rattue
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

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