Neurobiology of tau protein: 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 focus on 3 main research directions, performed mainly in vivo, with the help of transgenic mouse models of AD:

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 MT dependent axonal transport. Thus, we are studying the regulation of tau phosphorylation, tau splicing, and of tau toxicity and aggregation.
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 and biological susceptibilities such as aging, diabetes, inflammation, and external factors, such as anesthesia and trauma, on the development of tau pathology.
Pharmacological treatments of AD pathology
Targeting tauopathy with pharmacological compounds to alleviate the symptoms of AD is a growing field of research. We have been conducting research studying the impact of kinase inhibitors, as well as MT stabilizing drugs on tau pathology in vivo. We have now developed collaborations to study the effects of new compounds, and new therapeutic approaches.
All our research would not be possible without the support and generosity of the Alzheimer’s Society of Canada, the CIHR, the NSERC, the FRSQ, the RQRV, and AFIRMAQ.

CHUL
2705, boulevard Laurier
P-09717
Québec, Québec
Canada G1V 4G2
+1 418-525-4444, extension 47805 / 48639
+1 418-654-2753
emmanuel.planel@crchudequ... emmanuel.planel@neuroscie...

Latest news

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Tournissac M, Bourassa P, Martinez-Cano RD, Vu TM, Hebert SS, Planel E, Calon F

Repeated cold exposures protect a mouse model of Alzheimer's disease against cold-induced tau phosphorylation

Journal Article

Mol Metab, 22 , 2019.

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Muhire G, Iulita MF, Vallerand D, Youwakim J, Gratuze M, Petry FR, Planel E, Ferland G, Girouard H

Arterial Stiffness Due to Carotid Calcification Disrupts Cerebral Blood Flow Regulation and Leads to Cognitive Deficits

Journal Article

J Am Heart Assoc, 8 (9), 2019.

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Whittington RA, Virag L, Gratuze M, Lewkowitz-Shpuntoff H, Cheheltanan M, Petry F, Poitras I, Morin F, Planel E

Administration of the benzodiazepine midazolam increases tau phosphorylation in the mouse brain

Journal Article

Neurobiol Aging, 75 , 2019.

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Gratuze M, Josset N, Petry FR, Pflieger M, Eyoum Jong L, Truchetti G, Poitras I, Julien J, Bezeau F, Morin F, Samadi P, Cicchetti F, Bretzner F, Planel E

The toxin MPTP generates similar cognitive and locomotor deficits in hTau and tau knock-out mice

Journal Article

Brain Res, 1711 , 2019.

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Rodriguez L, Mdzomba JB, Joly S, Boudreau-Laprise M, Planel E, Pernet V

Corrigendum: Human Tau Expression Does Not Induce Mouse Retina Neurodegeneration, Suggesting Differential Toxicity of Tau in Brain vs. Retinal Neurons

Journal Article

Front Mol Neurosci, 11 , 2018.

Abstract | Links:

Rodriguez L, Mdzomba JB, Joly S, Boudreau-Laprise M, Planel E, Pernet V

Human Tau Expression Does Not Induce Mouse Retina Neurodegeneration, Suggesting Differential Toxicity of Tau in Brain vs. Retinal Neurons

Journal Article

Front Mol Neurosci, 11 , 2018.

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St-Amour I, Turgeon A, Goupil C, Planel E, Hebert SS

Co-occurrence of mixed proteinopathies in late-stage Huntington's disease

Journal Article

Acta Neuropathol, 135 (2), 2018.

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Whittington RA, Planel E, Terrando N

Impaired Resolution of Inflammation in Alzheimer's Disease: A Review

Journal Article

Front Immunol, 8 , 2017.

Abstract | Links:

Gratuze M, Julien J, Petry FR, Morin F, Planel E

Insulin deprivation induces PP2A inhibition and tau hyperphosphorylation in hTau mice, a model of Alzheimer's disease-like tau pathology

Journal Article

Sci Rep, 7 , 2017.

Abstract | Links:

Gratuze M, El Khoury NB, Turgeon A, Julien C, Marcouiller F, Morin F, Whittington RA, Marette A, Calon F, Planel E

Tau hyperphosphorylation in the brain of ob/ob mice is due to hypothermia: Importance of thermoregulation in linking diabetes and Alzheimer's disease

Journal Article

Neurobiol Dis, 98 , 2017.

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80 entries « ‹ 2 of 8 › »
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Active projects

  • Mechanisms of neuronal and vascular impairments in ischemic retinopathies, from 2019-04-01 to 2024-03-31
  • Microglial tau: a missing link between neuroinflammation and neurodegeneration in TDP-43 proteinopathies, from 2023-04-01 to 2028-03-31
  • Physiological regulation of tau protein, from 2023-04-01 to 2028-03-31
  • Prize - Mid Career Investigator Prize in Research in Aging: Microglial tau: a missing link between neuroinflammation and neurodegeneration in TDP-43 proteinopathies, from 2023-03-01 to 2024-02-29
  • Untangling tau contribution to cognitive impairments in Huntington’s disease., from 2019-04-01 to 2024-03-31

Recently finished projects

  • Neurobiologie de la protéine tau: régulation et dérégulation in vivo, from 2018-07-01 to 2022-06-30
  • Regulation of tau phosphorylation and splicing during post-embryonic development., from 2016-04-01 to 2022-03-31
  • Targeting tau pathology by modulating temperature, from 2018-07-01 to 2022-09-30
Data provided by the Université Laval research projects registery