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Research Grants 2016

To view an abstract, select an author from the vertical list on the left.

2016 Grants - Guo

Developing Protein Disaggregases and RNA Inhibitors for FTD Protein: FUS

Lin Guo, Ph.D.
University of Pennsylvania
Philadelphia, Pennsylvania

2016 Alzheimer’s Association Research Fellowship (AARF)

How do certain protein clumps promote frontotemporal dementia, and how may they be targeted to slow or prevent disease progression?

Frontotemporal dementia (FTD) is a neurodegenerative disease characterized by early-onset dementia with changes in personality and emotions. It gets its name from the fact that it affects the front and side (temporal) regions of the brain. FUS (an abbreviation for ‘fused in sarcoma’) is a protein implicated in the development of FTD. The FUS protein forms clumps in the brains of people with FTD, similar to the amyloid plaques formed from the clumping of beta-amyloid protein in the brains of people with Alzheimer’s disease. FUS normally binds to ribonucleic acid (RNA) a molecule involved in the production of proteins needed for normal cellular function. The clumping of FUS may impair its normal functions and promote nerve cell damage, but the underlying mechanisms are not yet understood.

Research Plan
Lin Guo, Ph.D., and colleagues will use novel molecular techniques and cells growing in laboratory dishes to study the formation of FUS protein clumps called aggregates. The will also test the effectiveness of different methods for inhibiting the formation of FUS clumps. One method involves proteins called “disaggregases” that may be able to effectively “break up” toxic FUS aggregates after they are formed. The other method will test whether treating the cells with molecules called RNA inhibitors, which can bind to FUS, can work to prevent or reverse the clumping process.

If successful, the work of Dr. Guo and colleagues could shed new light on how FUS protein accumulates in the brain in FTD. Importantly, this work may identify novel therapeutic strategies that target FUS to help slow or prevent disease progression.

Alzheimer's Association International Conference | July 16-20, 2017, London, England

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