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2008 Grants - Rylett
Modulation of Neuronal Gene Expression by Choline Acetyltransferase
Rebecca J. Rylett, Ph.D.
The University of Western Ontario
2008 Investigator-Initiated Research Grant
Nerve cells communicate with one another by secreting chemicals called neurotransmitters. Cholinergic neurons are nerve cells that use acetylcholine as their neurotransmitter. These neurons become particularly susceptible to damage in the early stages of Alzheimer's disease. Cholinergic neurons participate in many learning and memory functions that are known to decline as the disease progresses. So promoting the health of these neurons may prevent dementia or slow its progression.
Research has shown that the protein fragment beta-amyloid, a key suspect in Alzheimer's, may impair proper function in cholinergic neurons. Brain imaging research has found markedly reduced levels of acetylcholine in areas where beta-amyloid has accumulated.
Rebecca Jane Rylett, Ph.D., and colleagues have been studying the enzyme choline acetyltransferase (ChAT), which helps produce acetylcholine in cholinergic neurons. They have found that changes in cholinergic ChAT levels can alter the production of other molecules besides acetylcholine. Such changes likely occur early in Alzheimer's disease. For this study, the researchers plan to analyze how ChAT levels may affect the expression of proteins involved in Alzheimer's. Dr. Rylett's team believes that abnormally low ChAT production may increase levels of proteins involved in the release of beta-amyloid. The researchers will test their hypothesis using cultured cells and mice genetically engineered to develop varying levels of ChAT.
Results of this effort could lead to novel ways of diagnosing and treating Alzheimer's in its earliest stages.