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2005 Grant - D'Souza
Regulators of Tau mRNA and Protein Expression and Axonal Localization
Ian A. D'Souza, Ph.D.
Seattle Institute for Biomedical and Clinical Research
2005 New Investigator Research Grant
Neurofibrillary tangles, one of the two key features of Alzheimer's disease, are composed primarily of an abnormally altered protein called tau. These tangles, which occur within neurons in the brain, are also found in people who have other types of dementia. Although the appearance of neurofibrillary tangles seems to parallel neuronal loss as these diseases progress, it is not known exactly why the tangles form.
Ian A. D'Souza, Ph.D., and colleagues will study tau at the molecular level to understand why it forms tangles. They will focus on production of tau from its messenger RNA (mRNA), the genetic template that delivers a copy
of a gene's instructions for tau production to cellular components that actually assemble the protein.
In their studies, the researchers will use neurons grown in culture and genetically modified mice that produce human tau protein. They will try to identify what factors can influence production of the protein from its mRNA template. Because neurofibrillary tangles are predominantly found in axons, the long, thin fibers that carry electrical signals from one neuron to another, D'Souza and colleagues will examine if the protein template somehow becomes localized to these structures. They will examine where the tau template occurs in the cell during normal aging and disease, and they will try to identify mechanisms that influence this distribution. The study could identify factors that contribute to the formation of neurofibrillary tangles.