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Centre Hospitalier de l'Université Laval (CHUL)
2705, boulevard Laurier, RC-9800
CANADA G1V 4G2
- +1 418-525-4444, poste 47805
- +1 418-654-2753
Tau protein in neurobiology: regulation and deregulation in vivo
Alzheimer’s disease (AD) is the leading form of dementia. The neuropathological hallmarks of Alzheimer's disease include senile plaques of β-amyloid (Aβ) peptides (a cleavage product of the Amyloid Precursor Protein, or APP), and neurofibrillary tangles (NFT) of hyperphosphorylated tau protein assembled in paired helical filaments (PHF). NFT pathology is important since it correlates with the degree of cognitive impairment in AD. Our laboratory focuses on understanding the causes and consequences of tau pathology.
We have thus developped a research program examining the regulation of tau function in the normal brain, its deregulation in the diseased brain, with an emphasis on Alzheimer's disease (AD), and potential treatments available to alleviate tau pathology.
We focus on 3 main research directions, performed mainly in vivo, with the help of transgenic mouse models of AD:
1. Molecular basis of tau regulation in vivo
Hyperphosphorylation of tau by deregulation of kinases and/or phosphatases has been proposed to dissociate tau from microtubules (MTs), thereby destabilizing the MTs and disrupting MTdependent axonal transport. Thus, we are studying the regulation of tau phosphorylation, tau splicing and of tau toxicity and aggregation. This part of our research is financed by a NSERC grant.
2. Impact of biological and environmental factors on AD pathogenesis
Only a small proportion of AD is due to genetic variants, the large majority of cases (~95%) is late onset and sporadic in origin. The cause of sporadic AD is likely to be multifactorial, with external factors interacting with biological or genetic susceptibilities to accelerate the manifestation of the disease. Here, we study the impact of genetic (collaborative CIHR Grant with Dr. Judes Poirier, McGill) and biological susceptibilities such as aging (CIHR Pilot Grant), diabetes (CIHR grant), inflammation (collaborative ASC Grant with Dr. Jasna Kriz, ULaval) and external factors such as anesthesia (applied for a CIHR Grant), and trauma (collaborative CIHR Grant with Dr. Cheryl Wellington, UBC) on the development of AD pathology.
3. Pharmacological treatments of AD pathology
Targeting tauopathy with pharmacological compounds to alleviate the symptoms of AD is a growing research field. We have been conducting research studying the impact of kinases inhibitors, as well as MT stabilizing drugs on tau pathology in vivo. We have now developped collaborations to study the effects of new compounds, and new therapeutic approaches such as activators of phosphatases, ribozymes (Dr. Georges Lévesque, U. Laval) and micro RNAs (Dr. Sébastien Hébert, U. Laval) on tau pathogenesis.
All our research would not be possible without the support and generosity of the Alzheimer Society of Canada, the CIHR, the NSERC, the FRSQ, the RQRV and AFIRMAQ.
- Françoise MORIN, M.Sc.
- Jacinthe JULIEN, TSA
- Anastasia NOEL, Ph.D. (Alzheimer Society of Canada Fellowship)
- Franck PETRY, M.Sc. (Alzheimer Society of Canada Scholarship)
- Maya DICKLER, M.Sc. (NORAMPAC Scholarship, Alzheimer Society of Canada Scholarship)
- Maud GRATUZE, M.Sc.
- Geoffrey TRUCHETTI, D.V.M., M.Sc. (Didier Mouginot Scholarship)
- Isabelle POITRAS (B.Sc. Student, NSERC Scholarship)
- Jérôme PELLETIER (B.Sc. Student)
- Anne-Marie LAVIGNE (College Student)
- Ruben Dario MARTINEZ CANO (Trainee 2013, B.Sc. Student)
- Philippe MILOT-ROUSSEAU (Trainee 2013, B.Sc. Student)
- Noura EL KHOURY, M.Sc. (Ph.D. Student 2010-2013; Alzheimer Society of Canada Scholarship)
- François BEZEAU (Master Student, 2012-2013)
- Alexis BRETTEVILLE, Ph.D. (Post-doc, 2010-2012)
- Carl JULIEN, Ph.D. (Post-doc, 2010-2012; Alzheimer Society of Canada Fellowship)
- Marie-Amélie PAPON, Ph.D. (Post-doc, 2010-2011)
- Joanie BAILLARGEON, M.Sc. (Research Assistant, 2010-2011)
- François MARCOUILLER, M.Sc. (Master Student, 2009-2011)
- Alexandre LEMIEUX et Réda BENSAIDANE (Trainees 2010, College Students; Bronze Medal at the Canada-Wide Science Fair; 1st Place at the Sanofi-Aventis Biotalent Challenge)
Other active research project(s)
Georges Lévesque, Emmanuel Planel
Jasna Kriz, Emmanuel Planel