University of Pittsburgh researchers have developed a novel light-responsive tau protein (optoTAU) to allow for investigation of tau behavior in cells and to identify molecules that could modify tau aggregation in Alzheimer’s disease and other tauopathies. Dementias, including Alzheimer’s disease (AD) and other tauopathies and are defined by the presence of insoluble aggregates of the microtubule-associated protein, tau, in the brain. While there is a clear correlation between tau aggregates and symptoms in AD, understanding of the exact properties of tau that lead to neurotoxicity remain incomplete. Tau is a highly soluble protein that does not easily aggregate under native conditions. This novel tau model has been developed to allow understanding of the behavior of tau in living cells and which species or forms of tauare neurotoxic. Additionally, this clinical research model will be used to identify substances that can modify the aggregation tau, potentially reversing or preventing the development of dementias.
Applications/Indications
• Understanding the properties of tau aggregation in living cells
• Identifying modifiers of tau aggregation in living cells
• Improving the understanding of the role of tau in dementias and tauopathies
• Development of new pharmaceuticals to tackle dementia through modification of tau aggregationAdvantages
Dementia currently affects over 55 million people worldwide, with 10 million new cases each year. It is one of the leading causes of death and disability in older people and currently no cure exists. One major area of interest for researchers has been the role of tau aggregates in the development and progression of dementia. Currently, no tools exist to visualize or control the changes in tau behavior in live cells. OptoTAU can reproduce
the structural and biological properties of tau aggregation normally seen in the human brain, in live cells. This technology could allow researchers to gain a deeper understanding of the specific species of tau that induce neurotoxicity, and identify and optimize modifiers of tau behavior potentially leading to a cure for tau-related dementias.Invention Readiness
OptoTAU, a light-responsive tau protein, has been developed and shown to reproduce the biological and structural properties of tau aggregation observed in the human brain. Using viscosity-sensitive AggFluor probes, the causes and consequences of tau aggregation in human neurons have been investigated. OptoTAU can also be used to investigate the pathophysiological transition in tau solubility within living cells. OptoTAU can help identify modifiers of tau with the potential to be used as a pharmacological platform in novel drug discovery, or library screening of existing drugs.IP Status
Patent PendingInventors
Amantha Thathiah, PhD
Xin Zhang