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.
2705, boulevard Laurier
P-09717
Québec, Québec
Canada G1V 4G2
- Canet, GeoffreyPostdoctoral fellowCHUL+1 418-525-4444, extension 48639geoffrey.canet@crchudequebec.ulaval.ca
2705, boul. Laurier
P-09800
Québec, Québec
Canada G1V 4G2 - Diego Diaz, SofiaMaster studentCHUL+1 418-525-4444, extension 48639sofia.diego-diaz@crchudequebec.ulaval.ca
2705, boulevard Laurier
P-09800
Québec, QC
Canada G1V 4G2 - Fereydouni-Forouzandeh, ParissaMaster studentCHUL+1 418-525-4444, extension 48639parissa.fereydouni-forouzandeh@crchudequebec.ulaval.ca
2705, boulevard Laurier
P-09800
Québec, QC
Canada G1V 4G2 - Laliberté, FrancisEmployeeCHUL+1 418-525-4444, extension 48639francis.laliberte@crchudequebec.ulaval.ca
2705, boulevard Laurier
P-09800
Québec, QC
Canada G1V 4G2 - Rocaboy, EmmaMaster studentCHUL+1 418-525-4444, extension 48639emma.rocaboy@crchudequebec.ulaval.ca
2705, boulevard Laurier
P-09800
Québec, QC
Canada G1V 4G2
Differential Regulation of Tau Exon 2 and 10 Isoforms in Huntington's Disease Brain
Journal ArticleNeuroscience, 518 , 2023.
Intranasal Administration of Nanovectorized Docosahexaenoic Acid (DHA) Improves Cognitive Function in Two Complementary Mouse Models of Alzheimer's Disease
Journal ArticleAntioxidants (Basel), 11 (5), 2022.
Sauna-like conditions or menthol treatment reduce tau phosphorylation through mild hyperthermia
Journal ArticleNeurobiol Aging, 113 , 2022.
Seizure activity triggers tau hyperphosphorylation and amyloidogenic pathways
Journal ArticleEpilepsia, 63 (4), 2022.
Passive immunization against phosphorylated tau improves features of Huntington's disease pathology
Journal ArticleMol Ther, 30 (4), 2022.
Repurposing beta-3 adrenergic receptor agonists for Alzheimer's disease: beneficial effects in a mouse model
Journal ArticleAlzheimers Res Ther, 13 (1), 2021.
Metabolic determinants of Alzheimer's disease: A focus on thermoregulation
Journal ArticleAgeing Res Rev, 72 , 2021.
MicroRNA-138 Overexpression Alters Aβ42 Levels and Behavior in Wildtype Mice
Journal ArticleFront Neurosci, 14 , 2020.
Advances and Challenges in Understanding MicroRNA Function in Tauopathies: A Case Study of miR-132/212
Journal ArticleFront Neurol, 11 , 2020.
Circadian and sleep/wake-dependent variations in tau phosphorylation are driven by temperature
Journal ArticleSleep, 43 (4), 2020.
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