Madison Cornwell

TESTING THE SPECIFIC INHIBITION OF THE CDK5 AND GSK3-β KINASES IN THE 3XTG AD MOUSE MODEL TO STUDY THE FORMATION OF NEUROFIBRILLARY TANGLES

Many neurodegenerative diseases, including Alzheimer’s Disease (AD), Frontotemporal Dementia, and Niemann Pick Type C, are characterized by the histological finding of intracellular tau aggregates in the central nervous system termed “neurofibrillary tangles” (NFTs). Previous research has concluded that kinases such as CDK5 and GSK3-β are crucial to the development of tangles of hyperphosphorylated tau, and that these two kinases are up regulated in disease phenotypes. Consequently, inhibitors of these kinases may serve to ameliorate the symptoms of AD in patients. Currently, treatment of AD is restricted to drugs that increase the concentration of neurotransmitters to promote signaling between neurons. A drug targeting the cause of dementia has not been developed. We propose that specific inhibitors of CDK5 and GSK3-β may prove to be ideal candidates in the treatment of tauopathies. As a beginning step, we have demonstrated that two of these compounds are successful in clearing the brain of tau tangles in a 3XTg Alzheimer’s Disease Mouse Model.