2017-2018 Alzheimer’s and Related Diseases Research Award*Drug Repurposing for Tau Aggregation Inhibitors as Neuroprotective Agents for Alzheimer's Disease
*The Virginia Center on Aging which administers the Alzheimer’s and Related Diseases Research Award Fund for the Commonwealth of Virginia, provides seed money to researchers in Virginia to stimulate innovative research into biomedical and psychosocial aspects of dementia, including cell biology, caregiving, and animal modeling.
Drug Repurposing for Tau Aggregation Inhibitors as Neuroprotective Agents for Alzheimer’s Disease
Ling Wu, MD, PhD and Bin Xu, PhD
Virginia Tech University
AD is characterized by the accumulation of two types of abnormal structures, extracellular amyloid plaques and intraneuronal neurofibrillary tangles in brain. Small, soluble oligomers of the neuronspecific, axon-enriched, microtubule-associated protein, tau, the building blocks of the tangles, represent the most toxic molecular species in AD pathogenesis. Moreover, toxic, misfolded oligomers of both Aβ and tau self-propagate by prion-like processes, whereby their direct contact with normally folded counterparts catalyzes the latter’s conversion into toxic, misfolded forms. This project will screen repurposed drugs from an NIH Clinical Collection library of 700 small molecules and identify compounds that can block tau oligomer formation and protect neurons from tau-induced cytotoxicity. Further tests will establish whether validated lead compounds from the screens and additional in vitro assays can protect cultured neurons from the adverse effects of extracellular tau oligomers.
(Dr. Wu may be contacted at 540/231-8442, email@example.com; Dr. Xu may be contacted at 540/231-1449, firstname.lastname@example.org )
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