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Séminaire - Luc BuéeMicrotubule-associated tau proteins: from the good guy to the serial killer

Abstract :

Tau proteins were described in 1975 by Weingarten and coll. as a protein factor essential for microtubule assembly. There is now a large number of articles indicating the key role of tau proteins in microtubule polymerization and stabilization. In 1985, tau is found in neurofibrillary tangles in Alzheimer’s disease. In the following years, Tau is also described in a number of neurodegenerative disorders, in which Tau proteins aggregate, referred to as Tauopathies. The dark side of tau is definitely underlined in 1998 when mutations are discovered on the Tau gene, MAPT. However, such findings have allowed for the development of different experimental models (transgenesis, viral vectors…) and opened up new therapeutic avenues (A2A antagonists, cholesterol modulator, immunotherapy…). Finally, Tau has been recently described as a prion-like protein and raised the question of transmissibility…

 

L’équipe “Alzheimer & Tauopathies” s’intéresse à un mécanisme de mort des cellules nerveuses (neurones) du cerveau appelé dégénérescence neurofibrillaire. Cette dernière est caractérisée par l’accumulation et l’agrégation de protéines, les protéines Tau. Ce processus est observé dans la maladie d’Alzheimer et d’autres maladies neurodégénératives appelées Tauopathies. Les protéines Tau ont un rôle dans le transport intraneuronale, la plasticité synaptique et la protection contre les stress. Dans la maladie d’Alzheimer et les Tauopathies, ces fonctions sont perturbées suite à la modification et l’agrégation de ces protéines Tau.

Selected publications

Ahmed T, Blum D, Burnouf S, Demeyer D, Buée-Scherrer V, D’Hooge R, Buée L, Balschun D (2015) Rescue of impaired late-phase LTD in a tau transgenic mouse model. Neurobiol Aging, 36(2) 730-39.

Blum D, Herrera F, Gerhardt E, Francelle L, Basquin M, Obriot H, Sergeant N, Brouillet E, Buée L, Outeiro TF (2015) The impact of Huntingtin mutation on Tau phosphorylation and subcellular distribution. Hum Mol Genet, 24(1):76-85.

Caparros-Lefebvre D, Golbe LI, Deramecourt V, Maurage CA, Huin V, Buée-Scherrer V, Obriot H, Sablonnière B, Caparros F, Buée L, Lees AJ (2015) A geographical cluster of progressive supranuclear palsy in Northern France. Neurology, in press

Derisbourg M, Leghay C, Chiappetta G, Fernandez-Gomez FJ, Laurent C, Demeyer D, Carrier S, Buée-Scherrer V, Blum D, Vinh J, Sergeant N, Verdier Y, Buée L, Hamdane M (2015) Role of the Tau N-terminal region in microtubule stabilization revealed by new endogenous truncated forms. Sci Rep, 5:9659

Dujardin S, Colin M, Buée L (2015) Animal models of tauopathies and their implications for research/translation into the clinic. Neuropathol Appl Neurobiol, 41, 59–80

Duyckaerts C, Braak H, Brion JP, Buée L, Del Tredici K, Goedert M, Halliday G, Neumann M, Spillantini MG, Tolnay M, Uchihara T (2015) PART is part of Alzheimer disease. Acta Neuropathol, 129(5):749-56

Luc Buée's lab

Luc Buée is a French scientist (CNRS Research Director). Head of the Inserm laboratory « Alzheimer & Tauopathies » at the Jean-Pierre Aubert Research Centre, University of Lille, France. He has worked on Alzheimer disease and related disorders for more than  twenty five years. He started his work on the role of proteoglycans in Alzheimer's disease with a PhD training at Mount Sinai Medical Center, NYC. He was then involved in the initial characterization of tau aggregates among neurodegenerative disorders. He has then developed experimental models to better understand the role of post-translational modifications in tau aggregation. His group is currently working on the pathophysiological consequences of neurofibrillary degeneration and their links to the amyloid pathology in Alzheimer disease.   Luc Buée is also involved in different scientific advisory boards and operating committees in the field of AD. He has been recently nominated delegate at the Inserm Board for scientific evaluations in Neurosciences (CSS 6).