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2008 Grants - Taglialatela
Neurobehavioral Toxicity of Natural Amyloid-Beta Oligomers
Giulio Taglialatela, Ph.D.
University of Texas Medical Branch at Galveston
2008 Investigator-Initiated Research Grant
Beta-amyloid (also called amyloid-beta) is a protein fragment found in the brain that has long been suspected of playing a crucial role in Alzheimer's disease. In the brains of persons affected by the disease, beta-amyloid aggregates into large structures known as amyloid plaques, which are known to be toxic to nerve cells. In recent years, however, scientists have found evidence that smaller aggregates of beta-amyloid—known as oligomers and containing just a few particles of beta-amyloid—may be the cause of nerve cell dysfunction and cognitive deficits in Alzheimer's disease.
The mechanisms by which beta-amyloid oligomers cause nerve cell dysfunction are not known, but many scientists believe that blocking the action of these small aggregates may be a valuable way to slow or prevent the progression of Alzheimer's disease. Therefore, understanding how beta-amyloid oligomers cause nerve cell damage is of crucial importance.
Giulio Taglialatela, Ph.D., and colleagues are studying how beta-amyloid oligomers cause nerve cell dysfunction. The researchers have observed that an important brain enzyme known as calcineurin is increased in activity at the same time that levels of beta-amyloid oligomers increase and before amyloid plaques are formed. These findings were obtained from mice that had been genetically engineered to exhibit Alzheimer-like pathology. The researchers also found other evidence that calcineurin is activated by beta-amyloid oligomers, leading to nerve cell dysfunction.
Dr. Taglialatela and colleagues plan to use genetic engineering techniques to further explore the role of calcineurin in mediating the effects of beta-amyloid oligomers. They will use a mouse model in which they can control how much calcineurin is expressed. Using this system, they will test whether beta-amyloid oligomers are less toxic to nerve cell function when calcineurin levels are very low. These studies will help to identify how beta-amyloid oligomers cause nerve cell dysfunction, and they may help to identify a specific target for the development of future treatments for Alzheimer's disease.