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2008 Grants - Kim
Role of Rer1 in the Regulation of Gamma-Secretase Trafficking and Activity
Seong-Hun Kim, M.D., Ph.D.
University of Florida
2008 Investigator-Initiated Research Grant
The protein fragment beta-amyloid may disrupt cell-to-cell communication and cause cell death in Alzheimer's disease. Beta-amyloid is clipped from its parent molecule, amyloid precursor protein (APP), in a two-stage process. The second cut is made by a complex of proteins called gamma-secretase.
Two of the most important gamma-secretase proteins, presenilin 1 and presenilin 2, are encoded by the PS1 and PS2 genes. Mutations in PS1 and PS2 have been identified as factors in the development of familial, or inherited, Alzheimer's disease. However, other components of the gamma-secretase complex may also play decisive roles in Alzheimer pathology.
Seong-Hun Kim, M.D., Ph.D., and colleagues have been searching for novel Alzheimer-related components within gamma-secretase. Recently, the team analyzed a molecule called Rer1, which is involved in transporting gamma-secretase to different parts of a cell. This molecule may help enable the protein complex to produce beta-amyloid.
For their grant, Dr. Kim and colleagues will use cultured cells to determine how Rer1 might affect gamma-secretase's ability to produce beta-amyloid. In a related effort, the team will assess whether mutated PS1 genes also play a role in gamma-secretase transport, and whether the activities of PS1 mutants and Rer1 are interrelated.
Dr. Kim's work could reveal important information about the biological mechanisms underlying gamma-secretase activity. Such knowledge could reveal new therapeutic targets for preventing or treating Alzheimer's disease.