Protein in the brain could be a key target in controlling Alzheimer's
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.
"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 pathway and controls a biochemical chain reaction 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 plaque."
BACE-1 has long been a biological target for researchers seeking to create a drug against Alzheimer's disease, 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 brain," he said.
Journal reference: Annals of Neurology
Provided by Temple University
- Asthma drug could help control or treat Alzheimer's disease Mar 25, 2011 | not rated yet | 0
- Modulating a protein in the brain could help control Alzheimer's disease Nov 18, 2010 | not rated yet | 0
- Road block as a new strategy for the treatment of Alzheimer's Aug 22, 2011 | not rated yet | 0
- Study outlines how stroke, head injury can increase risk of Alzheimer's disease Jun 06, 2007 | not rated yet | 0
- Alzheimer's disease drug treats traumatic brain injury Jul 12, 2009 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
How can there be villous adenoma in colon, if there are no villi there
15 hours ago As title suggest. Thanks :smile:
How can there be a term called "intestinal metaplasia" of stomach
May 21, 2013 Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
Ratio of Hydrogen of Oxygen in Dessicated Animal Protein
May 13, 2013 As an experiment, for the past few months I've been consuming at least one portion of Jell-O or unflavored Knox gelatin per day. I'm 64, in very...
- More from Physics Forums - Medical Sciences
More news stories
(HealthDay)—Migraines and depression can each cause a great deal of suffering, but new research indicates the combination of the two may be linked to something else entirely—a smaller brain.
Neuroscience 6 hours ago | 5 / 5 (1) | 0 |
Moving objects attract greater attention – a fact exploited by video screens in public spaces and animated advertising banners on the Internet. For most animal species, moving objects also play a major ...
Neuroscience 9 hours ago | not rated yet | 0 |
It is known that signs of neurological disorders such as Alzheimer's and Huntington's disease can appear years before the disease becomes manifest; these signs take the form of subtle changes in the brain and behavior of ...
Neuroscience 9 hours ago | not rated yet | 0
Scientists have reversed behavioral and brain abnormalities in adult mice that resemble some features of schizophrenia by restoring normal expression to a suspect gene that is over-expressed in humans with ...
Neuroscience 10 hours ago | 5 / 5 (1) | 0 |
Researchers at Johns Hopkins have unraveled the molecular foundations of cocaine's effects on the brain, and identified a compound that blocks cravings for the drug in cocaine-addicted mice. The compound, already proven safe ...
Neuroscience 10 hours ago | not rated yet | 0 |
Swiss scientists reveal the mechanism responsible for aging hidden deep within mitochondria—and dramatically slow it down in worms by administering antibiotics to the young.
9 hours ago | 4.8 / 5 (5) | 0 |
Researchers from Queen Mary, University of London have led the largest sequencing study of human disease to date, investigating the genetic basis of six autoimmune diseases.
9 hours ago | 4 / 5 (1) | 0 |
Until now, little was scientifically known about the human potential to cultivate compassion—the emotional state of caring for people who are suffering in a way that motivates altruistic behavior.
6 hours ago | 5 / 5 (2) | 2 |
A new approach for immunizing against influenza elicited a more potent immune response and broader protection than the currently licensed seasonal influenza vaccines when tested in mice and ferrets. The vaccine ...
7 hours ago | not rated yet | 0 |
In a series of lab experiments designed to unravel the workings of a key enzyme widely considered a possible trigger of rheumatoid arthritis, researchers at Johns Hopkins have found that in the most severe ...
8 hours ago | 5 / 5 (1) | 0 |
Researchers have developed a new drug delivery system that allows inhalation of chemotherapeutic drugs to help treat lung cancer, and in laboratory and animal tests it appears to reduce the systemic damage ...
9 hours ago | not rated yet | 0 |