The relationship between truncation and phosphorylation at the C-terminus of tau protein in the paired helical filaments of Alzheimer's disease

Paola Flores-Rodríguez; Miguel A Ontiveros-Torres; María C Cárdenas-Aguayo; Juan P Luna-Arias; Marco A Meraz-Ríos; Amparo Viramontes-Pintos; Charles R Harrington; Claude M Wischik; Raúl Mena; Benjamin Florán-Garduño; José Luna-Muñoz

doi:10.3389/fnins.2015.00033

The relationship between truncation and phosphorylation at the C-terminus of tau protein in the paired helical filaments of Alzheimer's disease

Paola Flores-Rodríguez, Miguel A Ontiveros-Torres, María C Cárdenas-Aguayo, Juan P Luna-Arias, Marco A Meraz-Ríos, Amparo Viramontes-Pintos, Charles R Harrington, Claude M Wischik, Raúl Mena, Benjamin Florán-Garduño, José Luna-Muñoz

Instituto Politécnico Nacional

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Abstract

We previously demonstrated that, in the early stages of tau processing in Alzheimer's disease, the N-terminal part of the molecule undergoes a characteristic cascade of phosphorylation and progressive misfolding of the proteins resulting in a structural conformation detected by Alz-50. In this immunohistochemical study of AD brain tissue, we have found that C-terminal truncation of tau at Asp-421 was an early event in tau aggregation and analyzed the relationship between phospho-dependent tau epitopes located at the C-terminus with truncation at Glu-391. The aim of this study was to determine whether C-terminal truncation may trigger events leading to the assembly of insoluble PHFs from soluble tau aggregates present in pre-tangle cells. Our findings suggest that there is a complex interaction between phosphorylated and truncated tau species. A model is presented here in which truncated tau protein represents an early neurotoxic species while phosphorylated tau species may provide a neuroprotective role in Alzheimer's disease.

Original language	English
Article number	33
Number of pages	10
Journal	Frontiers in Neuroscience
Volume	9
DOIs	https://doi.org/10.3389/fnins.2015.00033
Publication status	Published - 11 Feb 2015

Bibliographical note

Acknowledgements:
Authors want to express their gratitude to Dr. P. Davies (Albert Einstein College of Medicine, Bronx, NY, USA) and Lester I. Binder (NorthWestern, Chicago, IL, USA) for the generous gift of mAbs (TG-3, Alz-50, and MC1), and (TauC-3), respectively, and to M. en C. Ivan J. Galván-Mendoza for his support in confocal microscopy, and Ms. Maricarmen De Lorenz for her secretarial assistance. We also want to express our gratitude to the Mexican Families who donate the brain of their loved ones affected with Alzheimer's disease, and made possible our research. This work was financially supported by CONACyT grant, No. 142293 (For R.M).

Keywords

tau protein
truncation
neurotoxicity
neurofibrillary tangles
PHFs
tau oligomers
Alzheimer's disease

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The relationship between truncation and phosphorylation at the C-terminus of tau protein in the paired helical filaments of Alzheimer's disease
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0/
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Charles Harrington
- School of Medicine, Medical Sciences & Nutrition, Neurosciences
- School of Medicine, Medical Sciences & Nutrition, Medical Sciences - Senior Research Fellow
- Institute of Medical Sciences
Person: Academic Related - Research
Claude Wischik
- School of Medicine, Medical Sciences & Nutrition, Neurosciences
- School of Medicine, Medical Sciences & Nutrition, Applied Medicine - Chair in Mental Health (Clin)
- Institute of Medical Sciences
Person: Clinical Academic

Cite this

Flores-Rodríguez, P., Ontiveros-Torres, M. A., Cárdenas-Aguayo, M. C., Luna-Arias, J. P., Meraz-Ríos, M. A., Viramontes-Pintos, A., Harrington, C. R., Wischik, C. M., Mena, R., Florán-Garduño, B., & Luna-Muñoz, J. (2015). The relationship between truncation and phosphorylation at the C-terminus of tau protein in the paired helical filaments of Alzheimer's disease. Frontiers in Neuroscience, 9, [33]. https://doi.org/10.3389/fnins.2015.00033

Flores-Rodríguez, P, Ontiveros-Torres, MA, Cárdenas-Aguayo, MC, Luna-Arias, JP, Meraz-Ríos, MA, Viramontes-Pintos, A, Harrington, CR , Wischik, CM, Mena, R, Florán-Garduño, B & Luna-Muñoz, J 2015, 'The relationship between truncation and phosphorylation at the C-terminus of tau protein in the paired helical filaments of Alzheimer's disease', Frontiers in Neuroscience, vol. 9, 33. https://doi.org/10.3389/fnins.2015.00033

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abstract = "We previously demonstrated that, in the early stages of tau processing in Alzheimer's disease, the N-terminal part of the molecule undergoes a characteristic cascade of phosphorylation and progressive misfolding of the proteins resulting in a structural conformation detected by Alz-50. In this immunohistochemical study of AD brain tissue, we have found that C-terminal truncation of tau at Asp-421 was an early event in tau aggregation and analyzed the relationship between phospho-dependent tau epitopes located at the C-terminus with truncation at Glu-391. The aim of this study was to determine whether C-terminal truncation may trigger events leading to the assembly of insoluble PHFs from soluble tau aggregates present in pre-tangle cells. Our findings suggest that there is a complex interaction between phosphorylated and truncated tau species. A model is presented here in which truncated tau protein represents an early neurotoxic species while phosphorylated tau species may provide a neuroprotective role in Alzheimer's disease.",

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note = "Acknowledgements: Authors want to express their gratitude to Dr. P. Davies (Albert Einstein College of Medicine, Bronx, NY, USA) and Lester I. Binder (NorthWestern, Chicago, IL, USA) for the generous gift of mAbs (TG-3, Alz-50, and MC1), and (TauC-3), respectively, and to M. en C. Ivan J. Galv{\'a}n-Mendoza for his support in confocal microscopy, and Ms. Maricarmen De Lorenz for her secretarial assistance. We also want to express our gratitude to the Mexican Families who donate the brain of their loved ones affected with Alzheimer's disease, and made possible our research. This work was financially supported by CONACyT grant, No. 142293 (For R.M).",

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AU - Cárdenas-Aguayo, María C

AU - Luna-Arias, Juan P

AU - Meraz-Ríos, Marco A

AU - Viramontes-Pintos, Amparo

AU - Harrington, Charles R

AU - Wischik, Claude M

AU - Mena, Raúl

AU - Florán-Garduño, Benjamin

AU - Luna-Muñoz, José

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N2 - We previously demonstrated that, in the early stages of tau processing in Alzheimer's disease, the N-terminal part of the molecule undergoes a characteristic cascade of phosphorylation and progressive misfolding of the proteins resulting in a structural conformation detected by Alz-50. In this immunohistochemical study of AD brain tissue, we have found that C-terminal truncation of tau at Asp-421 was an early event in tau aggregation and analyzed the relationship between phospho-dependent tau epitopes located at the C-terminus with truncation at Glu-391. The aim of this study was to determine whether C-terminal truncation may trigger events leading to the assembly of insoluble PHFs from soluble tau aggregates present in pre-tangle cells. Our findings suggest that there is a complex interaction between phosphorylated and truncated tau species. A model is presented here in which truncated tau protein represents an early neurotoxic species while phosphorylated tau species may provide a neuroprotective role in Alzheimer's disease.

AB - We previously demonstrated that, in the early stages of tau processing in Alzheimer's disease, the N-terminal part of the molecule undergoes a characteristic cascade of phosphorylation and progressive misfolding of the proteins resulting in a structural conformation detected by Alz-50. In this immunohistochemical study of AD brain tissue, we have found that C-terminal truncation of tau at Asp-421 was an early event in tau aggregation and analyzed the relationship between phospho-dependent tau epitopes located at the C-terminus with truncation at Glu-391. The aim of this study was to determine whether C-terminal truncation may trigger events leading to the assembly of insoluble PHFs from soluble tau aggregates present in pre-tangle cells. Our findings suggest that there is a complex interaction between phosphorylated and truncated tau species. A model is presented here in which truncated tau protein represents an early neurotoxic species while phosphorylated tau species may provide a neuroprotective role in Alzheimer's disease.

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KW - truncation

KW - neurotoxicity

KW - neurofibrillary tangles

KW - PHFs

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KW - Alzheimer's disease

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DO - 10.3389/fnins.2015.00033

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JO - Frontiers in Neuroscience

JF - Frontiers in Neuroscience

M1 - 33

ER -

The relationship between truncation and phosphorylation at the C-terminus of tau protein in the paired helical filaments of Alzheimer's disease

Abstract

Bibliographical note

Keywords

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Charles Harrington

Claude Wischik

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