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2010 Grants - Thathiah
Regulation of the Gamma-Secretase and Abeta Peptide Generation by GPR3
Amantha Thathiah, Ph.D.
2010 Mentored New Investigator Research Grant to Promote Diversity
Beta-amyloid (also known as Abeta) is a protein fragment at the focus of research into the causes of Alzheimer's disease. Scientists are studying many approaches to inhibit the production of beta-amyloid, including inhibition of the enzyme gamma-secretase, which cuts beta-amyloid from its precursor protein.
Amanda Thathiah, Ph.D., and colleagues have discovered a signaling protein named GPR3, which regulates the production of beta-amyloid, possibly by controlling the activity of gamma-secretase. In genetically altered mice that express Alzheimer pathology, removal of the gene for GPR3 reduces production of beta-amyloid. The researchers have also observed that GPR3 levels are high in parts of the brain showing Alzheimer pathology, and that some individuals with Alzheimer's disease have high levels of GPR3.
Dr. Thathiah and colleagues plan to expand their studies and test whether removal of the GPR3 gene in mice inhibits the formation of amyloid plaque, one of the hallmark features of Alzheimer pathology. They also plan to expand their studies of GPR3 levels in the brains of human patients with Alzheimer's disease and other neurodegenerative disorders, in order to determine whether GPR3 plays a role in these disorders. These studies will provide valuable insight into the roles of an important new signaling protein possibly involved in the development of Alzheimer pathology.