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

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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 languageEnglish
Article number33
Number of pages10
JournalFrontiers in Neuroscience
Volume9
DOIs
Publication statusPublished - 11 Feb 2015

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tau Proteins
Alzheimer Disease
Phosphorylation
Epitopes
Brain
Proteins

Keywords

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

Cite this

Flores-Rodríguez, P., Ontiveros-Torres, M. A., Cárdenas-Aguayo, M. C., Luna-Arias, J. P., Meraz-Ríos, M. A., Viramontes-Pintos, A., ... 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

The relationship between truncation and phosphorylation at the C-terminus of tau protein in the paired helical filaments of Alzheimer's disease. / Flores-Rodríguez, Paola; Ontiveros-Torres, Miguel A; Cárdenas-Aguayo, María C; Luna-Arias, Juan P; Meraz-Ríos, Marco A; Viramontes-Pintos, Amparo; Harrington, Charles R; Wischik, Claude M; Mena, Raúl; Florán-Garduño, Benjamin; Luna-Muñoz, José.

In: Frontiers in Neuroscience, Vol. 9, 33, 11.02.2015.

Research output: Contribution to journalArticle

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
Flores-Rodríguez P, Ontiveros-Torres MA, Cárdenas-Aguayo MC, Luna-Arias JP, Meraz-Ríos MA, Viramontes-Pintos A et al. 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. 2015 Feb 11;9. 33. https://doi.org/10.3389/fnins.2015.00033
Flores-Rodríguez, Paola ; Ontiveros-Torres, Miguel A ; Cárdenas-Aguayo, María C ; Luna-Arias, Juan P ; Meraz-Ríos, Marco A ; Viramontes-Pintos, Amparo ; Harrington, Charles R ; Wischik, Claude M ; Mena, Raúl ; Florán-Garduño, Benjamin ; Luna-Muñoz, José. / The relationship between truncation and phosphorylation at the C-terminus of tau protein in the paired helical filaments of Alzheimer's disease. In: Frontiers in Neuroscience. 2015 ; Vol. 9.
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AU - Luna-Arias, Juan P

AU - Meraz-Ríos, Marco A

AU - Viramontes-Pintos, Amparo

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AU - Wischik, Claude M

AU - Mena, Raúl

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N1 - 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).

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