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-09832
Québec, Québec
Canada G1V 4G2
83 entries « 1 of 9 »

Canet G, Rocaboy E, Diego-Diàz S, Whittington RA, Julien C, Planel E

Methods for Biochemical Isolation of Insoluble Tau in Rodent Models of Tauopathies

Journal Article

Methods Mol Biol, 2754 , 2024.

Abstract | Links:

Fereydouni-Forouzandeh P, Canet G, Diego-Diàz S, Rocaboy E, Petry S, Whittington RA, Planel E

Western Blot of Tau Protein from Mouse Brains Extracts: How to Avoid Signal Artifacts

Journal Article

Methods Mol Biol, 2754 , 2024.

Abstract | Links:

Canet G, Rocaboy E, Laliberté F, Boscher E, Guisle I, Diego-Diaz S, Fereydouni-Forouzandeh P, Whittington RA, Hébert SS, Pernet V, Planel E

Temperature-induced Artifacts in Tau Phosphorylation: Implications for Reliable Alzheimer's Disease Research

Journal Article

Exp Neurobiol, 32 (6), 2023.

Abstract | Links:

Petry S, Nateghi B, Keraudren R, Sergeant N, Planel E, Hébert SS, St-Amour I

Differential Regulation of Tau Exon 2 and 10 Isoforms in Huntington's Disease Brain

Journal Article

Neuroscience, 518 , 2023.

Abstract | Links:

Zussy C, John R, Urgin T, Otaegui L, Vigor C, Acar N, Canet G, Vitalis M, Morin F, Planel E, Oger C, Durand T, Rajshree SL, Givalois L, Devarajan PV, Desrumaux C

Intranasal Administration of Nanovectorized Docosahexaenoic Acid (DHA) Improves Cognitive Function in Two Complementary Mouse Models of Alzheimer's Disease

Journal Article

Antioxidants (Basel), 11 (5), 2022.

Abstract | Links:

Guisle I, Canet G, Pétry S, Fereydouni-Forouzandeh P, Morin F, Kérauden R, Whittington RA, Calon F, Hébert SS, Planel E

Sauna-like conditions or menthol treatment reduce tau phosphorylation through mild hyperthermia

Journal Article

Neurobiol Aging, 113 , 2022.

Abstract | Links:

Canet G, Zub E, Zussy C, Hernandez C, Blaquiere M, Garcia V, Vitalis M, deBock F, Moreno-Montano M, Audinat E, Desrumaux C, Planel E, Givalois L, Marchi N

Seizure activity triggers tau hyperphosphorylation and amyloidogenic pathways

Journal Article

Epilepsia, 63 (4), 2022.

Abstract | Links:

Alpaugh M, Masnata M, de Rus Jacquet A, Lepinay E, Denis HL, Saint-Pierre M, Davies P, Planel E, Cicchetti F

Passive immunization against phosphorylated tau improves features of Huntington's disease pathology

Journal Article

Mol Ther, 30 (4), 2022.

Abstract | Links:

Tournissac M, Leclerc M, Valentin-Escalera J, Vandal M, Bosoi CR, Planel E, Calon F

Metabolic determinants of Alzheimer's disease: A focus on thermoregulation

Journal Article

Ageing Res Rev, 72 , 2021.

Abstract | Links:

Tournissac M, Vu TM, Vrabic N, Hozer C, Tremblay C, Mélançon K, Planel E, Pifferi F, Calon F

Repurposing beta-3 adrenergic receptor agonists for Alzheimer's disease: beneficial effects in a mouse model

Journal Article

Alzheimers Res Ther, 13 (1), 2021.

Abstract | Links:

83 entries « 1 of 9 »
Signaler des ajouts ou des modifications

Active projects

  • 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

Recently finished projects

  • Mechanisms of neuronal and vascular impairments in ischemic retinopathies, from 2019-04-01 to 2024-03-31
  • Neurobiologie de la protéine tau: régulation et dérégulation in vivo, from 2018-07-01 to 2022-06-30
  • 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
  • Targeting tau pathology by modulating temperature, from 2018-07-01 to 2022-09-30
  • Untangling tau contribution to cognitive impairments in Huntington’s disease., from 2019-04-01 to 2024-03-31
Data provided by the Université Laval research projects registery