Project - Preclinical development of specific tau-binding compounds to target underlying disease mechanisms for the treatment of dementia
List all Chief investigators and associate investigators
- CIA Janet van Eersel
- CIB Lars Ittner
Research Project Abstract
Alzheimer’s disease and Frontotemporal Dementia are two of the most common causes of dementia. Unfortunately, there is currently no effective treatment or cure for either of these disorders. Therefore, the development and testing of new therapies is urgently required. Although these two dementias are quite distinct from one another, in both conditions, a protein known as Tau is thought to play a central role in the disease process. One mechanism by which Tau is thought to be involved, is via excessive interactions with another protein known as Fyn. Together, Fyn and Tau set off a cascade of events that lead to overstimulation of neuronal brain cells, eventually causing cell death. My work postulates that if interactions between Tau and Fyn could be disrupted or reduced in the brains of dementia patients, this would provide therapeutic benefits. Therefore, my research project aims to identify compounds that can disrupt interactions between Tau and Fyn by utilising a cutting-edge technology that can screen up to 14 billion compounds at once. Identified hits will then be tested in cell culture models to determine their potential usefulness. This will lay the groundwork for pre-clinical testing and, hopefully in the future, clinical trial testing in patients.
Project tag with a disease
Research Project Description
- DNA-encoded library screening
- In-vitro drug screening assays
Key Publications from this project
Ittner LM, Ke YD, Delerue F, Bi M, Gladbach A, van Eersel J, Wölfing H, Chieng BC, Christie MJ, Napier IA, Eckert A, Staufenbiel M, Hardeman E, Götz J. Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer's disease mouse models. Cell. 2010 Aug 6;142(3):387-97. doi: 10.1016/j.cell.2010.06.036. Epub 2010 Jul 22. PMID: 20655099.