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2016 Grants - Chakrabarty
Comparative Prionoid and Strain Properties of Tau and Synuclein
Paramita Chakrabarty, Ph.D.
University of Florida
2016 Alzheimer’s Association Research Grant (AARG)
Does the interaction of abnormal tau and alpha-synuclein proteins accelerate the progression of neurodegenerative disease?
A hallmark of many neurodegenerative diseases, including Alzheimer’s disease, is the accumulation of proteins into clumps in the brain that may interfere with nerve cell function. Three of these abnormal accumulations include: beta-amyloid which forms amyloid plaques, alpha-synuclein which forms Lewy bodies, and tau which forms “tangles.” In later stages of neurodegenerative diseases, the brain often contains a mixture of all three types of proteins. It is not yet clear what triggers the build-up of these proteins or how they may interact to accelerate disease progression.
Prions, which are small protein-like molecules, can form a “seed” that attracts other types of proteins to form toxic clumps. It is not known if certain types or “strains” of beta-amyloid, alpha-synuclein or tau protein also have seeding or “prionoid” properties. More research is needed to understand if there are common mechanisms that drive abnormal protein accumulation across neurodegenerative diseases.
Paramita Chakrabarty, Ph.D., and colleagues will investigate how tau and alpha-synuclein, either by themselves or together, act as seeds for the formation of protein clumps found in different types of neurodegenerative diseases. They will inject different disease-associated variations of tau and alpha-synuclein into the brains of mice and analzye which types trigger protein clumps. They will track the pattern by which the clumps “spread” throughout the brain and determine which types of nerve cells are most vulnerable to damage.
The results of these studies could provide new information on the molecular mechanisms that underlie the abnormal accumulation of proteins in the brain during Alzheimer’s and other neurodegenerative diseases. Importantly this work may guide the development of novel therapies that target the “seeding” process to prevent or slow disease progression.