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Title :

Molecular and cellular characterization of nanobodies directed against Tau

Date / Time:

22-02-2019 - 11:00

Type of seminar :

Seminar and meetings

Summary :

The aggregation of neuronal Tau protein to form fibrilar structures inside neurons is associated with tauopathies, notably Alzheimer’s disease (AD). A trans-synaptic transfer of Tau may participate in the spatio-temporal progression of the disease and this supposes that Tau is secreted into the interstitial fluids. Molecular and cellular mechanisms behind these processes, aggregation and transfer, are still unknown. Although Tau immunotherapy is a potential therapeutic strategy in AD, fundamental knowledge is still lacking to implement this strategy. We generated, characterized and optimized, in vitro and cellular assays, nanobodies targeted against Tau protein. As a starting point, in partnership with Hybribody, we obtained 19 VHHs against recombinant full-length Tau from a synthetic library. The recognition site of these VHHs on Tau was determined using NMR chemical shift perturbation experiments based on 1H,15N 2D spectra of Tau. We successfully defined the epitopes for 15 of them.Finally, a Tau fragment screening was performed by yeast two hybrids with the VHH F8-2 that allows to determine the minimal epitope for this VHH, confirming the epitope determined based on NMR data. These nanobodies will be used as molecular tools to decipher pathway(s) that might preferentially be altered in Tau immune strategy to block toxic propagation and aggregation

Name of speakers :

Dr Isabelle Landrieu

Speaker's affiliation :

CNRS de Lille

Address :

allée du 6-Août 17 4000 Liège
Bât. B7b
Floor number :0
Liège

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