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2011 Grants - Lahiri
Novel Regulation of APP and Beta-Secretase (BACE) in Alzheimer's Disease
Debomoy K. Lahiri, Ph.D.
2011 Investigator-Initiated Research Grant
Amyloid precursor protein (APP) is the parent molecule of beta-amyloid, a fragment of APP that aggregates into amyloid plaques, one of the characteristic features of Alzheimer's pathology. The production of beta-amyloid from APP is performed by a series of enzymes, cutting proteins, of which beta-secretase (BACE1) is a key component.
Increases in beta-amyloid levels in the brain in persons with Alzheimer's disease may involve abnormal expression of APP or BACE1. Little is known, however, about how the expression of these key proteins is regulated in nerve cells of the brain.
Debomoy K. Lahiri, Ph.D. and colleagues are studying how the expression of APP and BACE1 are regulated by molecules known as microRNA. MicroRNA bind to regions of genetic material that control the expression of proteins. The researchers have proposed to identify and characterize microRNA that regulate the expression of APP and BACE1. They will then study how these microRNA interact with other signaling pathways that help to regulate the expression of these proteins. The researchers will examine how dysfunction of microRNA regulation affects the levels of beta-amyloid in nerve cells. Finally, Dr. Lahiri's team will study whether the microRNA they have identified in cell studies are expressed in persons with Alzheimer's disease and in healthy controls. These studies may provide insight into the regulation of beta-amyloid levels, and they may suggest potential targets for drugs to reduce the accumulation of this protein fragment.