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2009 Grants - Rogers
Post-Transcriptional Control of Alzheimer's APP and Brain Iron Homeostasis
Jack T. Rogers, Ph.D.
Massachusetts General Hospital
Candidate for 2009 Zenith Fellows Award
The protein fragment beta-amyloid is thought to play a key role in hindering cell-to-cell communication and causing brain cell death in Alzheimer's disease. This fragment is clipped from its parent molecule, amyloid precursor protein (APP), and it tends to produce clumps called plaques in the Alzheimer brain. Another likely feature of Alzheimer's is the excessive brain accumulation of iron. Studies have shown that high iron levels cause brain cell damage well before the appearance of amyloid plaques.
Jack T. Rogers, Ph.D., and colleagues have found that iron helps regulate a part of the genetic process by which APP is produced. This part involves the "translation" of APP from its gene through messenger ribonucleic acid (mRNA). MRNA is a kind of genetic "photocopy" that delivers a gene's protein-building instructions to cellular components that assemble the protein. Because iron may regulate the production of APP, it also may help control the subsequent clipping of beta-amyloid from APP. Thus if iron levels in the brain become too high, similar increases in APP and beta-amyloid levels may also occur.
For this grant, the researchers hope to verify that iron-regulatory protein-1, the molecule that controls the proper storage of iron in the brain, may also help regulate the production of both APP and beta-amyloid. The findings of this study could lead to new mRNA-based therapies for reducing beta-amyloid levels in Alzheimer's, Down syndrome and other related neurological disorders.