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2011 Grants - Ansari
The Complex Role of NADPH-Oxidase (NOX) in Alzheimer's Disease
Mubeen Ansari, Ph.D.
University of Kentucky Research Foundation
2011 New Investigator Research Grant
NADPH-Oxidase (NOX) is an enzyme or cutting protein present in nearly all cells which is important for many normal processes, including nerve signaling and blood vessel function. However, NOX also generates oxidative chemical groups that can damage cells and cellular functions.
Mubeen Ansari, Ph.D. and colleagues have recently found evidence that increasing levels of NOX in a region of the brain known as the prefrontal cortex are associated with worse scores on tests of brain function in older adults. Other studies have also linked oxidative stress with increases in cellular pathology or brain change associated with Alzheimer's disease.
Dr. Ansari and colleagues have proposed detailed studies to examine changes in NOX activity and brain structure in a region of the brain known as the ventral medial temporal lobe (vMTL). This region is known to be affected in the early stages of Alzheimer's disease. The researchers will obtain brain samples from persons who died with specific brain pathologies that often precede Alzheimer's disease. They will use biochemical techniques to measure levels of NOX activity in the vMTL.
Dr. Ansari's team will also measure levels of proteins found in brain synapses, as a way to measure the health of synapses. This aspect of the study is important because synapses are specialized regions of brain cells responsible for rapid signaling, as well as many aspects of learning and memory. Furthermore, synapses represent some of the earliest sites of damage in Alzheimer's disease. Finally, the researchers will study the activity of a protein known as cofilin, which is critical for maintaining nerve cell structure, including synapses. These studies will allow the researchers to explore whether oxidative damage associated with NOX causes damage to synapses, and whether that damage involves dysfunction of cofilin. The results may provide new insights into the pathology of Alzheimer's disease and may help to define the causes of early cognitive decline during the first stages of disease.