- Aberrant tau phosphorylation by glycogen synthase kinase-3beta and JNK3 induces oligomeric tau fibrils in COS-7 cells
Laboratory for Alzheimer s Disease, Brain Science Institute, RIKEN, 2 1 Hirosawa, Wako Shi, Saitama 351 0198, Japan
J Biol Chem 277:42060-5. 2002
..These results suggest that aberrant tau phosphorylation by the combination of these kinases may be involved in "pretangle," oligomeric tau fibril formation in vivo...
- Alterations in glucose metabolism induce hypothermia leading to tau hyperphosphorylation through differential inhibition of kinase and phosphatase activities: implications for Alzheimer's disease
Laboratory for Alzheimer s Disease, The Institute of Physical and Chemical Research, Wako Shi, Saitama 351 0198, Japan
J Neurosci 24:2401-11. 2004
..Our results imply that serine-threonine protein phosphatase 2A plays a major role in regulating tau phosphorylation in the adult brain and provide in vivo evidence for its crucial role in abnormal tau hyperphosphorylation in AD...
- A neuronal microtubule-interacting agent, NAPVSIPQ, reduces tau pathology and enhances cognitive function in a mouse model of Alzheimer's disease
Department of Neurology, Georgetown University Medical Center, 4000 Reservoir Road N W, Washington, DC 20057, USA
J Pharmacol Exp Ther 325:146-53. 2008
..Our results suggest that neuronal microtubule interacting agents such as NAP may be useful therapeutic agents for the treatment or prevention of tauopathies...
- Interplay between cyclin-dependent kinase 5 and glycogen synthase kinase 3 beta mediated by neuregulin signaling leads to differential effects on tau phosphorylation and amyloid precursor protein processing
Taub Institute at Columbia University Medical Center, New York State Psychiatric Institute, New York, New York 10032, USA
J Neurosci 28:2624-32. 2008
..Thus, cdk5 inhibitors may not be effective in targeting tau phosphorylation in the elderly...
- Transcriptional regulation of beta-secretase by p25/cdk5 leads to enhanced amyloidogenic processing
Taub Institute at Columbia University Medical Center, New York, NY 10032, USA
Neuron 57:680-90. 2008
..These data demonstrate a pathway by which p25/cdk5 increases the amyloidogenic processing of APP through STAT3-mediated transcriptional control of BACE1 that could have implications for AD pathogenesis...
- Hypothermia-induced hyperphosphorylation: a new model to study tau kinase inhibitors
Universite Laval, Faculte de Medecine, Département de Neurosciences et Psychiatrie
Sci Rep 2:480. 2012
..Therefore, we propose hypothermia-induced hyperphosphorylation as a reliable, fast, convenient and inexpensive tool to screen for tau kinase inhibitors...
- Alzheimer's disease and anesthesia
Marie Amélie Papon
Département de Psychiatrie et Neurosciences, Centre Hospitalier de l Université Laval Québec, QC, Canada
Front Neurosci 4:272. 2011
..Here, we review the literature linking anesthesia to AD, with a focus on the biochemical consequences of anesthetic exposure on AD pathogenic pathways...
- Deregulation of protein phosphatase 2A and hyperphosphorylation of τ protein following onset of diabetes in NOD mice
Marie Amélie Papon
Centre hospitalier de l Universite Laval, Axe Neurosciences, Quebec, Canada
Diabetes 62:609-17. 2013
..This model may be a useful tool to address further mechanistic association between insulin dysfunction and AD pathology...
- Insulin dysfunction induces in vivo tau hyperphosphorylation through distinct mechanisms
Laboratory for Alzheimer s Disease, The Institute of Physical and Chemical Research, Saitama 351 0198, Japan
J Neurosci 27:13635-48. 2007
- Anesthesia leads to tau hyperphosphorylation through inhibition of phosphatase activity by hypothermia
Columbia University Medical Center, Department of Pathology, Taub Institute for Alzheimer s Disease Research, New York, New York 10032, USA
J Neurosci 27:3090-7. 2007
..Furthermore, a thorough examination of the effect of anesthesia-induced hypothermia on the risk and progression of AD is warranted...
- Anesthesia-induced hyperphosphorylation detaches 3-repeat tau from microtubules without affecting their stability in vivo
Taub Institute for Alzheimer s Disease Research, Department of Pathology, Columbia University Medical Center, New York, New York 10032, USA
J Neurosci 28:12798-807. 2008
..Tau remaining on the MTs under these conditions is sufficient to maintain MT network integrity...
- Acceleration and persistence of neurofibrillary pathology in a mouse model of tauopathy following anesthesia
Axe Neurosciences, Centre hospitalier de l Universite Laval, Universite Laval, Quebec, Quebec, Canada
FASEB J 23:2595-604. 2009
- c-jun N-terminal kinase hyperphosphorylates R406W tau at the PHF-1 site during mitosis
Laboratory for Alzheimer s Disease, Brain Science Institute, The Institute of Physical and Chemical Research RIKEN, Saitama, Japan
FASEB J 20:762-4. 2006
- Dimethyl sulfoxide induces both direct and indirect tau hyperphosphorylation
Département de Neurosciences et Psychiatrie, Faculte de Medecine, Universite Laval, Quebec, Quebec, Canada
PLoS ONE 7:e40020. 2012
..These data should caution researchers working with DMSO as it can induce artifactual results both in vivo and in vitro...
- Gene network and pathway analysis of mice with conditional ablation of Dicer in post-mitotic neurons
Axe Neurosciences, Centre de Recherche du CHUQ CHUL, Quebec, Quebec, Canada
PLoS ONE 7:e44060. 2012
..To date, however, little is known about the genes and molecular networks regulated by neuronal miRNAs in vivo, particularly in the adult mammalian brain...
- MicroRNA-132 loss is associated with tau exon 10 inclusion in progressive supranuclear palsy
Pascal Y Smith
Centre de recherche du CHUQ, Axe Neurosciences, Quebec, Canada
Hum Mol Genet 20:4016-24. 2011
..Taken together, these results suggest that changes in the miR-132/PTBP2 pathway could contribute to the abnormal splicing of tau exon 10 in the brain, and sheds light into the potential role played by miRNAs in a subset of tauopathies...
- Anesthesia-induced hypothermia mediates decreased ARC gene and protein expression through ERK/MAPK inactivation
Robert A Whittington
Department of Anesthesiology, Columbia University Medical Center, New York, NY, USA
Sci Rep 3:1388. 2013
..These data give new mechanistic insights on the regulation of immediate early genes by anesthesia and hypothermia. ..
- A transgenic rat that develops Alzheimer's disease-like amyloid pathology, deficits in synaptic plasticity and cognitive impairment
Department of Pathology, Taub Institute for Research on Alzheimer s Disease, Columbia University, Black Building 5 513, 650 West 168th Street, New York, NY 10032, USA
Neurobiol Dis 31:46-57. 2008
- Tau filament formation and associative memory deficit in aged mice expressing mutant (R406W) human tau
Laboratory for Alzheimer s Disease and Neural Architecture, Brain Science Institute, Institute of Physical and Chemical Research RIKEN, 2 1 Hirosawa, Wako Shi, Saitama 351 0198, Japan
Proc Natl Acad Sci U S A 99:13896-901. 2002
- Genetic ablation of Dicer in adult forebrain neurons results in abnormal tau hyperphosphorylation and neurodegeneration
Sébastien S Hébert
Centre de Recherche du CHUQ CHUL, Axe Neurosciences, Quebec, Canada
Hum Mol Genet 19:3959-69. 2010
..In summary, these results support the hypothesis that changes in the miRNA network may contribute to a neurodegenerative phenotype by affecting tau phosphorylation...
- Specificity of anti-tau antibodies when analyzing mice models of Alzheimer's disease: problems and solutions
Franck R Petry
Universite Laval, Faculte de Medecine, Départment de Psychiatrie et Neurosciences, Quebec, Canada Centre de recherche du CHU de Québec, CHUL, Axe Neurosciences, Quebec, Canada
PLoS ONE 9:e94251. 2014
..We strongly recommend the use of negative (i.e., TKO) and positive (i.e., hypothermic) controls in all experiments...
- Propofol directly increases tau phosphorylation
Robert A Whittington
Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, New York, New York, United States of America
PLoS ONE 6:e16648. 2011
- Cognitive and non-cognitive behaviors in the triple transgenic mouse model of Alzheimer's disease expressing mutated APP, PS1, and Mapt (3xTg-AD)
Neurobehavioral Phenotyping Platform, Department of Molecular Medicine, Laval University and Laboratory of Endocrinology and Genomics, CHUQ Research Center, 2705 Blvd Laurier, Quebec, QC G1V 4G2, Canada
Behav Brain Res 234:334-42. 2012
..On the contrary, the mutants did not differ from controls in pain thresholds, nest-building, and various reflexes determined by the SHIRPA primary screen and were even better on the rotorod test of motor coordination...
- Retromer deficiency observed in Alzheimer's disease causes hippocampal dysfunction, neurodegeneration, and Abeta accumulation
Taub Institute for Research on Alzheimer s Disease and the Aging Brain, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
Proc Natl Acad Sci U S A 105:7327-32. 2008
..By recapitulating features of the disease, these animal models suggest that retromer deficiency observed in late-onset Alzheimer's disease can contribute to disease pathogenesis...
- Metabolic activity determines efficacy of macroautophagic clearance of pathological oligomeric alpha-synuclein
Wai Haung Yu
Dept of Pathology, Columbia University Medical Center, 630 W168th St Rm 12 461, New York NY 10032, USA
Am J Pathol 175:736-47. 2009
..This study provides therapeutic and pathological implications for both synucleinopathy and Parkinson's disease, identifying conditions in which autophagy may be insufficient to degrade alpha-syn aggregates...
- ERK (MAPK) does not phosphorylate tau under physiological conditions in vivo or in vitro
Département de Psychiatrie et Neurosciences, Faculte de Medecine, Universite Laval, Quebec, Quebec, Canada Centre Hospitalier de l Université Laval, Axe Neurosciences, Quebec, Quebec, Canada
Neurobiol Aging 36:901-2. 2015
..Finally, ERK1/2 was inhibited, but tau phosphorylation was not altered in Mek1-/- mice. In conclusion, these results do not support the involvement of ERK1/2 in tau phosphorylation under physiological conditions. ..
- Biochemical isolation of insoluble tau in transgenic mouse models of tauopathies
Axe Neurosciences, Centre hospitalier de l Universite Laval, Quebec, QC, Canada
Methods Mol Biol 849:473-91. 2012
- In vivo turnover of tau and APP metabolites in the brains of wild-type and Tg2576 mice: greater stability of sAPP in the beta-amyloid depositing mice
Nathan Kline Institute for Psychiatric Research, Orangeburg, New York, USA
PLoS ONE 4:e7134. 2009
..Given the neurotrophic roles attributed to sAPP, the enhanced stability of sAPP in the beta-amyloid depositing Tg2576 mice may represent a neuroprotective response...
- Tau aggregates: toxic, inert, or protective species?
Columbia University Medical Center, Taub Institute for Research on Alzheimer s Disease and the Aging Brain, New York, NY 10032, USA
J Alzheimers Dis 14:431-6. 2008
..Here, we will first examine tau aggregation and its putative roles in Alzheimer's disease. We will then review the findings concerning different species of tau and their potential toxicity...
- Tau hyperphosphorylation and deregulation of calcineurin in mouse models of Huntington's disease
Département de Psychiatrie et Neurosciences, Universite Laval, Quebec, QC, Canada Axe Neurosciences, Centre de Recherche du CHU de Québec, Quebec, QC, Canada
Hum Mol Genet 24:86-99. 2015
..Taken together, our data suggest that mutant huntingtin can induce abnormal tau hyperphosphorylation in vivo, via the deregulation of calcineurin. ..
- Hypothermia and Alzheimer's disease neuropathogenic pathways
R A Whittington
Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, 622 West 168th Street PH 5, New York, NY 10032, USA
Curr Alzheimer Res 7:717-25. 2010
..Here, we review the preclinical data involving hypothermia with tau and Aβ, as well as clinical evidence implicating hypothermia in the development of AD...
- Inhibition of glycogen synthase kinase-3 by lithium correlates with reduced tauopathy and degeneration in vivo
Center for Dementia Research, Nathan S Kline Institute, New York University, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA
Proc Natl Acad Sci U S A 102:6990-5. 2005
..These results support the idea that kinases are involved in tauopathy progression and that kinase inhibitors may be effective therapeutically...
- Untangling memory deficits
Nat Med 11:826-7. 2005
- U-box protein carboxyl terminus of Hsc70-interacting protein (CHIP) mediates poly-ubiquitylation preferentially on four-repeat Tau and is involved in neurodegeneration of tauopathy
Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Fukuoka, Japan
J Neurochem 91:299-307. 2004
..Thus, CHIP is a ubiquitin ligase for four-repeat tau and maintains neuronal survival by regulating the quality control of tau in neurons...