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2009 Grants - Leznick
Role of SUMOylation in Alzheimer's Diseases
Elena Leznick, Ph.D.
Columbia University Medical Center
New York, New York
2009 New Investigator Research Grant
After proteins are made inside cells, they are often modified by the attachment of large organic molecules. This process is an important way for the cell to control a protein's function and location. One type of modification is called SUMOylation (SUMO is an acronym for small ubiquitin-like modifiers). SUMOylation of proteins serves a number of important cellular functions, and there is evidence that it plays a role in some cellular models of learning and memory.
Beta-amyloid is a protein fragment that aggregates into clusters that are toxic to nerve cells. Beta-amyloid also blocks some forms of plasticity in the brain that are important for learning and memory. Elena Leznick, Ph.D. and colleagues have found that stimulation of SUMOylation can reverse this detrimental effect of beta-amyloid.
The researchers plan to perform more detailed studies of the role of SUMOylation using mice that have been genetically altered to express Alzheimer-like pathology. They will study whether stimulation of SUMOylation in these animals can reverse some of the detrimental effects of Alzheimer-like pathology on brain plasticity and memory. The researchers will also examine biochemical changes occurring during disease progression and whether SUMOylation plays a role in those changes. These studies will advance our understanding of biochemical mechanisms leading to dysfunction of nerve cells in Alzheimer's disease.