Role of a Novel Protein, PSAP, in Neurodegeneration
Ph.D., Institute of Technology, Japan
More than 15 million people worldwide suffer from the devastating effects of Alzheimer’s disease, which is characterized by plaques and tangled bundles of fibers in and around the brain cells. These plaques are made up of beta amyloid, a toxic protein fragment cleaved from a larger protein called amyloid precursor protein, or APP. The tangled fibers form following changes in tau, a protein involved in intracellular transport.
Genetic analysis of the familial form of Alzheimer’s disease has resulted in the identification of three causative genes: APP, presenilin 1, and presenilin 2. Among these causative genes, mutations in presenilin 1 account for the majority of known cases of familial Alzheimer’s disease. APP, a protein found in brain cells, is necessary for normal brain function. Although its exact function is unknown, research indicates that APP protects brain cells from injury.
Researchers know that presenilins, proteins found in brain cells, interact with many signaling pathways; however, the exact function of these proteins is largely unknown. Researchers suspect that presenilin 1 plays a role in apoptosis, or programmed cell death, one of the mechanisms of neuronal cell death observed in Alzheimer’s disease.
Dr. Xu’s group has identified a novel protein, presenilin-associated protein (PSAP) that interacts with the C-terminal of presenilin 1 and causes cell death when over expressed. Dr. Xu’s finding establishes, for the first time, a molecular link between presenilin 1 and an apoptotic cascade.
Cleavage of APP is crucial in the pathogenesis of Alzheimer’s disease; researchers suspect that presenilin 1 has an important role in regulating the enzyme that cleaves APP into beta amyloid pieces. Currently, Dr. Xu is making significant progress elucidating the molecular roles of presenilin 1 and PSAP in the formation of beta amyloid, and the mechanisms by which gamma-secretase processes APP to produce the pathogenic beta amyloid peptide.
Results from Dr. Xu’s studies may provide new therapeutic targets for the design of treatments for Alzheimer’s disease.