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2008 Grants - Guillemin
Identification of a New Neurodegenerative Mechanism in Alzheimer's Disease
Gilles J. Guillemin, Ph.D.
The University of New South Wales
2008 Investigator-Initiated Research Grant
Cell-to-cell communication in the brain depends on the sending and receiving of messenger chemicals. Cells transmit messenger chemicals using receptors, or "docking sites," on their surface. Studies have shown that overactivation of the N-methyl-D-aspartate (NMDA) receptor, a docking site for the memory-related messenger chemical glutamate, may result in nerve cell death during Alzheimer's disease.
Gilles J. Guillemin, Ph.D., and colleagues have identified a substance that may help cause overactivation of NMDA receptors. This substance, called excitotoxin quinolinic acid (QUIN), is released by immune system cells known as macrophages and microglia. In preliminary studies with mice, Dr. Guillemin's team found that elevated levels of beta-amyloid in the brain led to a significant production of QUIN. Beta-amyloid is a protein fragment that may be involved in Alzheimer's. Further research determined that QUIN may help produce abnormal forms of the protein tau in human nerve cells. Abnormal tau clumps together into harmful tangles within the Alzheimer brain.
For their proposed study, Dr. Guillemin and colleagues will further analyze the relationships between QUIN and various Alzheimer-related proteins. Using mice genetically engineered to develop Alzheimer-like symptoms, the researchers will administer drugs known to inhibit the production of QUIN and other similar molecules. They will then determine whether these dugs also reduce beta-amyloid and abnormal tau levels in the mice. Results of Dr. Guillemin's study could identify a novel therapeutic strategy for the treatment of Alzheimer's disease.