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LEGHAY Coline (INSERM U1172 éq. 01 - Malika HAMDANE)
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@mail :  malika.hamdane@inserm.fr      tél. :  0632599858


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Titre de la communication :
Functional investigation of new N-terminally truncated Tau species and relevance to Alzheimer\'s disease
Auteurs (et leurs adresses) de la communication :
Coline Leghay, Maxime Derisbourg, Dominique Demeyer, David Blum, Valérie Buée-Scherrer, Vincent Deramecourt, Luc Buée & Malika Hamdane Equipe Alzheimer & Tauopathies, UMR-S 1172 Inserm, Univ.Lille 2, CHU Lille, Centre de Recherche Jean-Pierre AUBERT
Résumé de la communication :
Background: Tau protein plays an important role in Alzheimer\'s Disease (AD) where it is found aggregated and abnormally modified in degenerating neurons. Moreover, truncation is among post-translational modifications of Tau and its role in AD pathological process is far from being elucidated. Recently, we have identified new N-terminally truncated Tau species (Trunc-Tau) from human brain. Among them, the N-terminally Trunc-Tau starting at Methionine11 (Met11-Tau) was also found with a post-translational modifications that has never been described for Tau (Mod-Met11-Tau).
Objective: Our work aims to: 1) perform functional characterization of Met11-Tau and to study the new post-translational modification; 2) establish whether there is an association between the level of Met11-Tau and/or modified form and Tau pathology.
Results: On one hand, we have established inducible stable cell lines expressing the full length-Tau protein (FL-Tau) and the Met11-Tau in order to analyze functional consequences of Met11-Tau expression, compared to its related FL-Tau (Western Blot, fractionation, confocal microscopy and Elisa assay). Moreover, this cell lines have allowed to identify the enzyme responsible for the new modification and are used to determine the role of the new modification on Met11-Tau degradation, subcellular localization and aggregation. We expect to uncover the functional impact of truncation at Met11 and the new modification on Tau protein.
On the other hand, we succeeded in development of a specific monoclonal antibody targeting Mod-Met11-Tau. we are using this specific monoclonal antibody to analyze by Immunohistochemistry (IHC) the immunolabeling pattern in controls and AD patients. Our preliminary data showed that this antibody specifically labels AD brains. This tool will be used in IHC on human brains samples to establish whether Mod-Met11-Tau is a signature feature of AD and other Tauopathies.
Conclusion: This work will determine the role of Met11-Tau and its modification, it will thus provide new knowledge on Tau biology and the physiopathological process of AD.

Acknowledgements:
PhD student funding: Doctoral grant co-sponsored by the Région Nord/Pas-de-Calais & CHU-Lille.
We thank Raphaelle Caillierez, Sébastien Carrier and Sabiha Eddarkoui for technical help, the Lille NeuroBank (CHU-Lille) for providing brain tissues, Plate-forme Imagerie cellulaire de Lille 2 for confocal microscopy (Meryem Tardivel). This work is supported by the Université Lille 2, Inserm, RégionNord/Pas-de-Calais, FEDER, and the Labex DISTALZ.

LEGHAY Coline (INSERM U1172 éq. 01 - Malika HAMDANE)