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2014 Grants - Wolozin
It Takes TIA to Tangle: The Role of RNA Binding Proteins in Alzheimer’s
Benjamin Wolozin, M.D., Ph.D.
2014 Zenith Fellows Award
Neurofibrillary tangles, often referred to as “tangles,” are one of the characteristic brain changes in Alzheimer’s disease. Tangles are made from abnormal clumps of the protein tau, which normally functions as part of the cell structure and machinery to transport nutrients throughout the cell. The mechanisms that trigger the formation of tangles are not well understood.
RNA (ribonucleic acid) is a long-stranded molecule that performs several functions in the cell, but one of its most prominent functions is to carry the genetic code from the genes in your DNA (deoxyribonucleic acid) to the machinery for making proteins. Several proteins bind to RNA, also known as RNA-binding proteins, some of which are responsible for making sure the RNA is folded into the right shape to make it function correctly. In some situations, such as when cells are under stress, RNA-binding proteins form clumps that store RNA for later use; these clumps are known as stress granules.
Benjamin Wolozin, Ph.D., and colleagues have found evidence that tau binds to specific RNA binding proteins in stress granules. The researchers will study how RNA-binding proteins change the characteristics of tau, and potentially increase its tendency to form tangles.
Using mice that have been genetically altered to develop tangles, Dr. Wolozin’s team will also study whether RNA-binding proteins and stress granules are more common in mice that form tangles. Additionally, they will investigate the relationship between these proteins, stress granules and tau during disease progression. These studies will advance our knowledge of how tangles form, and they may provide clues about strategies to prevent their formation and ultimately suggest a novel therapeutic target.