Скачать или смотреть 14-3-3/Tau: The Way to an Alzheimer's Cure?

This animation was prepared in support of a grant project proposal submitted in response to an STW Open Mind call back in 2015. In previous work we developed a small molecule inhibitor of the protein-protein interaction (PPI) between adapter protein, 14-3-3, and hyperphoshorylated full length Tau (pTau) in vitro. This intermediate result is significant because 14-3-3 binding to pTau is hypothesized to destabilize microtubule formation in neurons as a potential molecular basis for neurodegeneration in Alzheimer’s patients. The objective of the grant proposal was therefore to obtain timely funding for a team of master students to develop a cell permeable variant of our inhibitor and to test whether inhibition of 14-3-3/Tau inhibition can also be achieved within the complex environment of the cell – a crucial next step toward establishing the 14-3-3/Tau hypothesis. Regrettably, our proposal was not funded. However, since submitting the proposal Femke Meijer and Sebastian Andrei, PhD students in the Chemical Biology group, have succeeded in developing a library of more potent analogs of our initial inhibitor in vitro, and are characterizing the binding modes of these new inhibitors by X-ray crystallography.

For more information, see:
Y. Joo, B. Schumacher, I. Landrieu, M. Bartel, C. Smet-Nocca, A. Jang, H.S. Choi, N.L. Jeon, K.-A. Chang, H.-S. Kim, C. Ottmann, Y.-H. Suh, FASEB J. 2015, 29(10), 4133-4144 (https://doi.org/10.1096/fj.14-265009).
L.-G. Milroy, M. Bartel, M.A. Henen, S. Leysen, J.M. Adriaans, L. Brunsveld, I. Landrieu, C. Ottmann, Angew. Chem. Int. Ed. 2015, 54(52), 15720-15724 (https://doi.org/10.1002/anie.201507976).

Credits:
Animation: ICMS Animation Studio
Voice-over: Studio Make